Study of Quasielastic Barrier Distributions as a Step towards the Synthesis of Superheavy Elements with Hot Fusion Reactions.

The excitation functions for quasielastic scattering of ^{22}Ne+^{248}Cm, ^{26}Mg+^{248}Cm, and ^{48}Ca+^{238}U are measured using a gas-filled recoil ion separator. The quasielastic barrier distributions are extracted for these systems and are compared with coupled-channel calculations. The results indicate that the barrier distribution is affected dominantly by deformation of the actinide target nuclei, but also by vibrational or rotational excitations of the projectile nuclei, as well as neutron transfer processes before capture. From a comparison between the experimental barrier distributions and the evaporation residue cross sections for Sg (Z=106), Hs (108), Cn (112), and Lv (116), it is suggested that the hot fusion reactions take advantage of a compact collision, where the projectile approaches along the short axis of a prolately deformed nucleus. A new method is proposed to estimate the optimum incident energy to synthesize unknown superheavy nuclei using the barrier distribution.

On the adsorption and reactivity of element 114, flerovium.

Flerovium (Fl, element 114) is the heaviest element chemically studied so far. To date, its interaction with gold was investigated in two gas-solid chromatography experiments, which reported two different types of interaction, however, each based on the level of a few registered atoms only. Whereas noble-gas-like properties were suggested from the first experiment, the second one pointed at a volatile-metal-like character. Here, we present further experimental data on adsorption studies of Fl on silicon oxide and gold surfaces, accounting for the inhomogeneous nature of the surface, as it was used in the experiment and analyzed as part of the reported studies. We confirm that Fl is highly volatile and the least reactive member of group 14. Our experimental observations suggest that Fl exhibits lower reactivity towards Au than the volatile metal Hg, but higher reactivity than the noble gas Rn.

First Study on Nihonium (Nh, Element 113) Chemistry at TASCA.

Nihonium (Nh, element 113) and flerovium (Fl, element 114) are the first superheavy elements in which the 7p shell is occupied. High volatility and inertness were predicted for Fl due to the strong relativistic stabilization of the closed 7p 1/2 sub-shell, which originates from a large spin-orbit splitting between the 7p 1/2 and 7p 3/2 orbitals. One unpaired electron in the outermost 7p 1/2 sub-shell in Nh is expected to give rise to a higher chemical reactivity. Theoretical predictions of Nh reactivity are discussed, along with results of the first experimental attempts to study Nh chemistry in the gas phase. The experimental observations verify a higher chemical reactivity of Nh atoms compared to its neighbor Fl and call for the development of advanced setups. First tests of a newly developed detection device miniCOMPACT with highly reactive Fr isotopes assure that effective chemical studies of Nh are within reach.

Production cross sections of Mo, Nb and Zr radioisotopes from α-induced reaction on natZr.

Cross sections of α-induced reactions on natural zirconium were measured up to 50 MeV using the stacked-foil technique, activation method and high resolution γ-ray spectrometry. The production cross sections of 93m,99Mo, 90g,92m,95g,95m,96Nb and 88,89g,95Zr were determined and compared with other experimental data measured earlier and result of theoretical calculations. The integral thick target yield of 99Mo was deduced from the measured cross section data.

Biochemical and cellular activity of chemically synthesized elastase inhibitor (S-AFUEI) from Aspergillus fumigatus.

PURPOSE: Elastase, produced by Aspergillus fumigatus and A. flavus, is an important pathogenic factor in pulmonary aspergillosis. We investigated the possibility of using A. fumigatus-derived A. fumigatus elastase inhibitor (AFUEI) as a therapeutic agent. As native-AFUEI (N-AFUEI) has an extremely low yield, we generated a synthetic-AFUEI (S-AFUEI) and investigated whether S-AFUEI has a biological activity against A. fumigatus elastase (AFUE) and inhibits cytotoxicity. METHODOLOGY: A. fumigatus was cultured in Yeast Carbon Base (YCB) -elastin culture medium for 3-7 days, and AFUE was purified by chromatography using DE52 cellulose and Sephadex G-75 column. Elastolytic activity was examined using Glt-Ala-Ala-Pro-Leu-pNA (GAAPLNA) as the substrate. The hydrolytic activity of AFUE was determined using the characteristic substrates, fibrinogen and collagen (Type IV), and human cell cytotoxicity was measured colorimetrically. Furthermore, the inhibitory effect of S-AFUEI on these activities was examined. RESULTS: We confirmed that S-AFUEI demonstrated elastase inhibitory activity and heat stability equivalent to that demonstrated by N-AFUEI, and inhibited human collagen hydrolytic activity and human fibrinogen hydrolytic activity. Further, S-AFUEI inhibited cytotoxicity in AFUE human pulmonary artery endothelial cells (HPAEC), human small airway epithelial cells (HSAEC), and human pulmonary alveolar epithelial cells (HPAEpiC). CONCLUSION: As S-AFUEI strongly inhibited cytotoxicity induced by elastase in human-derived cells, it could prove beneficial for the treatment of pulmonary aspergillosis.

Measurement of activation cross sections of alpha particle induced reactions on iridium up to an energy of 50 MeV.

Cross sections of alpha particle induced nuclear reactions on iridium were investigated using a 51.2-MeV alpha particle beam. The standard stacked-foil target technique and the activation method were applied. The activity of the reaction products was assessed without chemical separation using high resolution gamma-ray spectrometry. Excitation functions for production of gold, platinum and iridium isotopes (196m2Au, 196m,gAu, 195m,gAu, 194Au, 193 m,gAu, 192Au, 191m,gAu, 191Pt, 195mPt, 194gIr, 194mIr, 192gIr, 190gIr and 189Ir) were determined and compared with available earlier measured experimental data and results of theoretical calculations using TALYS code system. Cross section data were reported for the first time for the natIr(α,x)196m2Au, natIr(α,x)196m,gAu, natIr(α,x)191Pt, natIr(α,x)195mPt, natIr(α,x)194gIr, natIr(α,x)194mIr, natIr(α,x)190gIr and natIr(α,x)189Ir processes. A possible production route for 195mPt, the potentially important radionuclide in nuclear medicine, is discussed.

Production cross sections of 169Yb and Tm isotopes in deuteron-induced reactions on 169Tm.

The excitation functions of deuteron-induced reactions on 169Tm were measured using the stacked-foil method and high resolution gamma-ray spectrometry. The production cross sections of a medical radionuclide 169Yb were investigated. The result was compared with the previous experiments and found to be in good agreement. In addition to 169Yb, the production cross sections of Tm isotopes, 170Tm, 168Tm and 167Tm, were measured. These results were compared with the TALYS calculations taken from the TENDL-2015 online data library.

Clinical significance of fucose level in glycoprotein fraction of serum in patients with malignant tumors.

Serum fucose content in the glycoprotein fraction was determined in various patients with malignant and benign diseases. The results showed that, in contrast to benign diseases, malignant diseases were characterized by an increased fucose content in the glycoprotein fraction. However, no significant difference was noted in the fucose levels in the mucoprotein fraction. The increased fucose level in glycoprotein in malignant diseases was parallel to the increment in total fucose content in serum, which suggests that the increased levels in total fucose in malignant diseases, reported previously, are primarily due to the increase in fucose-containing glycoprotein.

Neuropeptide Y signaling in the dorsal raphe nucleus inhibits male sexual behavior in mice.

Animals change their biological activities depending on their nutritional state. Reproductive functions, including sexual behavior, are suppressed under low-energy conditions; however, the underlying neuronal mechanism is poorly understood. Neuropeptide Y (NPY) is an orexigenic molecule released in response to low-energy conditions and has an inhibitory effect on sexual behavior. We examined how NPY is involved in energy state-dependent regulation of male sexual behavior. Mounting, intromission, and ejaculation were evaluated as parameters of sexual behavior. Almost all parameters indicated that fasting for 24h suppressed male sexual behavior. Intracerebroventricular injection of NPY inhibited sexual behavior in males that free-fed for 8h following 24-h fasting (fed males). We next examined whether the dorsal raphe nucleus (DRN), in which serotonergic (5-HT) neurons are distributed, is involved in NPY-mediated inhibition of male sexual behavior. NPY-positive processes immunoreactive for a presynaptic marker, synaptophysin, were distributed in the DRN of both fed and fasted males. Expression of the NPY Y1 receptor in 5-HT neurons was also observed. Direct injection of NPY or 8-OH-DPAT (a 5-HT1A receptor agonist that inhibits the activity of 5-HT neurons) into the DRN inhibited male sexual behavior in fed males. In contrast, injection of BIBP-3226, a NPY Y1 receptor antagonist, or (+)-DOI hydrochloride (DOI), a 5-HT2A/2C receptor agonist that activates 5-HT neurons, into the DRN partially recovered male sexual behavior in 24-h fasted males. These results suggest that NPY inhibits serotonergic neuronal activity via the Y1 receptor in the DRN, resulting in suppression of male sexual behavior in low-energy conditions.

Cross section measurement of alpha particle induced nuclear reactions on natural cadmium up to 52MeV.

Cross sections of alpha particle induced nuclear reactions have been measured on thin natural cadmium targets foils in the energy range from 11 to 51.2MeV. This work was a part of our systematic study on excitation functions of light ion induced nuclear reactions on different target materials. Regarding the cross sections, the alpha induced reactions are not deeply enough investigated. Some of the produced isotopes are of medical interest, others have application in research and industry. The radioisotope 117mSn is a very important theranostic (therapeutic + diagnostic) radioisotope, so special care was taken to the results for that isotope. The well-established stacked foil technique followed by gamma-spectrometry with HPGe gamma spectrometers were used. The target and monitor foils in the stack were commercial high purity metal foils. From the irradiated targets 117mSn, 113Sn, 110Sn, 117m,gIn, 116mIn, 115mIn, 114mIn, 113mIn, 111In, 110m,gIn, 109mIn, 108m,gIn, 115gCd and 111mCd were identified and their excitation functions were derived. The results were compared with the data of the previous measurements from the literature and with the results of the theoretical nuclear reaction model code calculations TALYS 1.8 (TENDL-2015) and EMPIRE 3.2 (Malta). From the cross section curves thick target yields were calculated and compared with the available literature data.

Biochemical and physiological studies on a kallikrein-like enzyme from the venom of Crotalus viridis viridis (prairie rattlesnake).

A kallikrein-like enzyme was isolated from Crotalus viridis viridis (Prairie rattlesnake) venom by Sephadex G-50, DEAE-Sephacel and heparin-Sepharose CL-6B column chromatography. The purified enzyme has a molecular mass of 32 kDa and an isoelectric point of 5.4. The enzyme catalyzed the hydrolysis of arginine esters, kallikrein substrates Pro-Phe-Arg-MCA and Z-Phe-Arg-MCA. The specificity of the enzyme's substrate requirement is demonstrated by the fact that no proteolytic activity was detected against either dimethyl casein or fibrinogen. The enzyme also cleaves kininogen analogs to release bradykinin. Although the enzyme induced contraction of the isolated rat uterus directly at high concentrations, more forceful contractions resulted when the reaction mixture of the enzyme and bovine plasma was applied to the uterus. The reaction mixture of 5.10(-11) M of the enzyme and plasma caused contractions equal to that of 10(-9) M of bradykinin. Additionally the enzyme demonstrated capillary permeability-increasing activity and hypotensive activity on the anesthetized rat, suggesting that the enzyme releases the dilator of the wall of capillaries from plasma. Uterine contraction, capillary permeability-increasing activity and arginine esterolytic activity were inhibited by diisopropyl fluorophosphate, indicating that the serine hydroxyl group is essential for enzymatic and biological activities. It was demonstrated that the NH2-terminal region of the enzyme has significant similarities in sequence with kallikrein-like enzymes from other snake venoms and porcine pancreatic kallikrein.

Specificity of hemorrhagic proteinase from Crotalus atrox (western diamondback rattlesnake) venom.

Hemorrhagic proteinase, HTb, isolated from Crotalus atrox (western diamondback rattlesnake) venom was studied for its specificity. HTb showed fibrinogenase activity, hydrolyzing the A alpha chain of fibrinogen first, followed by the cleavage of the B beta chain. HTb is different from thrombin and did not produce a fibrin clot. The degradation products of fibrinogen were found to be different, indicating that the cleavage sites in the A alpha and B beta chains are different from those of thrombin. N-Benzoyl-Phe-Val-Arg-p-nitroanilide was not hydrolyzed by HTb, although this substrate was hydrolyzed by thrombin and reptilase.

Brain dysfunction associated with an induction of nitric oxide synthase following an intracerebral injection of lipopolysaccharide in rats.

We investigated the pathophysiological role of nitric oxide synthesized by inducible nitric oxide synthase in the brain, by injecting lipopolysaccharide directly into the rat cerebral cortex/hippocampus. The levels of nitric oxide metabolites, nitrite and nitrate, began to increase in a dose-dependent manner with a 3-h lag, and reached approximately seven-fold the basal levels 8 h after the direct injection of lipopolysaccharide (5 microg). The lipopolysaccharide-induced increase in nitrite and nitrate levels was inhibited by treatment with the specific inducible nitric oxide synthase inhibitor aminoguanidine. The protein synthesis inhibitor cycloheximide delayed the onset of the increase in nitric oxide metabolite levels, and reduced the peak levels. Lipopolysaccharide increased Ca2+-independent, but not Ca2+-dependent, nitric oxide synthase activity in the brain. Intense nicotinamide adenine dinucleotide phosphate-diaphorase activity was observed in round cells in the vicinity of the site of injection of lipopolysaccharide 8 h after the injection. Neuronal death was observed seven days after the injection of lipopolysaccharide. Spatial memory, as assessed by performance in a water maze task and spontaneous alternation behavior in a Y-maze, was significantly impaired in rats which had had previous bilateral injections of lipopolysaccharide into the hippocampus. The lipopolysaccharide-induced neuronal death and spatial memory impairments were prevented by aminoguanidine. These results suggest that direct injection of lipopolysaccharide into the brain causes an induction of inducible nitric oxide synthase in vivo. Furthermore, it is suggested that nitric oxide produced by inducible nitric oxide synthase is responsible for the lipopolysaccharide-induced brain dysfunction.

Role of nitric oxide and cyclic GMP in the dizocilpine-induced impairment of spontaneous alternation behavior in mice.

The activation of N-methyl-D-aspartate receptors induces the synthesis of nitric oxide, which activates soluble guanylate cyclase and leads to the formation of cyclic GMP in the brain. The inhibition of nitric oxide production, as well as the blockade of N-methyl-D-aspartate receptors, has been reported to prevent the induction of hippocampal long-term potentiation and learning and memory formation in vivo, although the effects of inhibitors of nitric oxide synthase are still controversial. We investigated the putative role of nitric oxide and cyclic GMP in dizocilpine-induced memory impairment in mice. The nitric oxide synthase inhibitors, NG-nitro-L-arginine methyl ester and 7-nitro indazole, as well as dizocilpine, a non-competitive N-methyl-D-aspartate receptor antagonist, dose-dependently impaired spatial working memory in mice, assessed by their spontaneous alternation behavior in a Y-maze. The inhibitory effects of both NG-nitro-L-arginine methyl ester and dizocilpine on their behavior were completely reversed by 8-bromo-cyclic GMP. Cyclic GMP levels in the cerebellum were reduced by treatment with dizocilpine. NG-Nitro-L-arginine methyl ester and 7-nitro indazole reduced cyclic GMP levels in the cerebral cortex/hippocampus and cerebellum, and the suppressive effect of NG-nitro-L-arginine methyl ester on cyclic GMP levels in the cerebral cortex/hippocampus was reversed by co-treatment with L-arginine. Cyclic AMP levels in the brain were not affected by treatment with either dizocilpine, NG-nitro-L-arginine methyl ester, or 7-nitro indazole. Neither NG-nitro-L-arginine methyl ester nor L-arginine had any effect on monoamine and acetylcholine metabolism in the brain. These results suggest that the reduction in nitric oxide/cyclic GMP production in the brain may be responsible for dizocilpine-induced impairment of spontaneous alternation behavior in a Y-maze.

Role of nitric oxide in learning and memory and in monoamine metabolism in the rat brain.

1. We investigated the effects of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthase, on the performance of rats in a radial arm maze and in habituation tasks, and on monoamine metabolism in the brain. 2. Daily administration of L-NAME (10-60 mg kg-1) resulted in a dose-dependent impairment of performance during the acquisition of the radial arm maze task, while it failed to affect performance in those rats that had previously acquired the task. 3. The rate of decrease in locomotor activity in the habituation task in the L-NAME-treated rats was significantly less than that in control rats. 4. NG-nitro-D-arginine methyl ester (D-NAME, a less active inhibitor of NO synthase) showed no effects in the above behavioural tasks. 5. NO synthase activity was significantly decreased in both the L-NAME and D-NAME-treated rats, with the magnitude of inhibition being greater in the L-NAME-treated animals. 6. The content of 5-hydroxyindoleacetic acid (5-HIAA) in the hippocampus and the 5-HIAA/5-hydroxytryptamine ratio in the hippocampus and cortex were significantly decreased in the L-NAME (60 mg kg-1)-treated rats compared with these values in the controls. 7. Striatal 3,4-dihydroxyphenylacetic acid (DOPAC) content was significantly increased in the L-NAME (60 mg kg-1)-treated rats compared with the values in the controls, while the DOPAC/dopamine ratio was not changed. 8. These results suggest that: (i) NO may play an important role in performance during the acquisition,but not retention, of the radial arm maze task, and (ii) that endogenous NO may be involved in the regulation of monoamine metabolism.

Role of nitric oxide in the development of tolerance and sensitization to behavioural effects of phencyclidine in mice.

1. To determine whether nitric oxide (NO) was involved in tolerance and sensitization to the effects of phencyclidine (PCP), we examined NO synthase activity and the number of NADPH-diaphorase (NADPH-d)-positive cells in discrete brain regions of saline-, acute PCP- and repeated PCP-treated mice. We also investigated the effects of a NO synthase inhibitor, NG-nitro-L- arginine methyl ester (L-NAME), on the behavioural changes induced by repeated PCP treatment in mice. 2. Acute PCP (1, 3, and 10 mg kg-1, s.c.) treatment induced dose-dependent hyperlocomotion, motor incoordination and stereotyped behaviours, consisting of sniffing, head movement and ataxia in mice. 3. In mice treated repeatedly with PCP (1, 3, and 10 mg kg-1 day-1), s.c., once a day for 14 days), the sniffing, head movement, ataxia and motor incoordination induced by PCP were attenuated (indicating the development of tolerance to these behaviours), whereas the hyperlocomotion induced by PCP was potentiated (indicating the development of sensitization to hyperlocomotion). The development of tolerance and sensitization to PCP-induced behaviours in the repeated PCP-treated mice was more marked at the dose of 10 mg kg-1 day-1) than at other doses. 4. NO synthase activity in the cerebral cortex and cerebellum, but not in the striatum and hippocampus, was significantly decreased by acute PCP (10 mg kg-1) treatment in comparison with saline treatment, and such changes in activity in the cerebral cortex and cerebellum were reversed by repeated PCP treatment (10 mg kg-1 day-1). 5. The number of neurones containing NADPH-d reactivity in the cerebral cortex, nucleus accumbens, and striatum of acute and repeated PCP-treated mice showed no change in comparison with saline-treated mice. 6. Tolerance to PCP (10 mg kg-1 day-1)-induced ataxia and motor incoordination was significantly attenuated by combined treatment with L-NAME (50 mg kg-1 day-1 i.p.). 7. Sensitization to PCP-induced hyperlocomotion was further enhanced by combined treatment with L-NAME (50 mg kg-1 day-1). However, NG-nitro-D-arginine methyl ester (D-NAME, 50 mg kg-1 day-1, i.p.), a less active enantiomer of L-NAME, had no effect, suggesting a stereospecific mechanism. 8. The PCP-induced behaviours in animals that had exhibited tolerance and sensitization to PCP (10 mg kg-1 day-1) were not influenced by acute L-NAME (5 and 50 mg kg-1, i.p.) or D-NAME (50 mg kg-1, i.p.) treatment. 9. These results suggest that NO may play an important role in the development, but not in the maintenance, of tolerance and sensitization to the effect of PCP in mice.

The role of thiols in the apparent activation of rat brain nitric oxide synthase (NOS).

The role of thiols on the activation and/or stabilization of rat brain nitric oxide synthase (NOS) has been investigated. It was found that thiols are not necessary for stabilizing or protecting the protein during purification but are required during enzyme turnover for maximum activity. In the complete absence of thiols but with added tetrahydrobiopterin, the enzyme retained a low basal activity. Thiol addition to a thiol-deplete preparation of the enzyme resulted in a 4 to 7-fold increase in activity when measured after 15 min. High concentrations of dihydropteridine reductase also caused an apparent activation of NOS and was capable of replacing thiols. The data presented is consistent with a cofactor role for thiols. The possibility that they serve as reducing agents for the regeneration of tetrahydrobiopterin from dihydrobiopterins is discussed.

Structural analysis of the amyloidogenic kappa Bence Jones protein (FUR).

Patients with systemic amyloidosis associated with multiple myeloma (AL-amyloidosis) exhibit immunoglobulin light chains and fragments which have been identified as amyloid protein. Since a relatively small proportion of patients with multiple myeloma develop AL-amyloidosis, comparison of the amino acid sequence of the amyloidogenic and non-amyloidogenic immunoglobulin light chains and the structural characterization of the amyloid proteins are required to understand the relationship between structure and amyloidogenicity. We determined the primary structure of a kappa I-type Bence Jones protein obtained from a patient (FUR) who had systemic AL-amyloidosis associated with multiple myeloma. We identified eight amino acid replacements unique to this patient among the amyloidogenic kappa I-light chains, and which are also rare among the known kappa type light chains of humans. Three of these substitutions were within the framework regions and may act to destabilize the structure to promote a putative amyloidogenic conformation. In contrast to light chain fragments in the urine, which were processed in the variable region, mass spectrometric analysis of the fibril proteins isolated from lingual amyloid deposits in this patient, revealed that they were all truncated within the constant region and corresponded to residues 1-125, 1-144, and 1-210. Inspection of the predicted three-dimensional model of this protein suggested that these fragments may be generated by a protease specific for the N-terminal sides of basic amino acids. These findings suggest that amino acid substitutions at highly conserved residues may convert non-amyloidogenic to amyloidogenic immunoglobulin light chain proteins.

Construction of a series of mutants lacking all of the four major mex operons for multidrug efflux pumps or possessing each one of the operons from Pseudomonas aeruginosa PAO1: MexCD-OprJ is an inducible pump.

We constructed a series of deletion mutants lacking all of the four major mex operons for Mex multidrug efflux pumps or possessing each one of the operons from Pseudomonas aeruginosa PAO1. The drug specificity of MexAB-OprM, MexXY-OprM and MexCD-OprJ was investigated. Surprisingly, we found that the MexCD-OprJ was an inducible pump, inducers of which were tetraphenylphosphonium chloride, ethidium bromide, rhodamine 6G and acriflavine. Fluoroquinolones, chloramphenicol, erythromycin and tetracycline were not inducers although they were substrates of MexCD-OprJ.

Reduction in the number of NADPH-diaphorase-positive cells in the cerebral cortex and striatum in aged rats.

Nitric oxide (NO) plays an important role as a diffusible messenger in learning and memory. To determine whether changes in NO production in the brain may be involved in aging-associated brain dysfunction, we measured the performance of aged rats in a radial arm maze task, and carried out histochemical examination of the changes in NADPH diaphorase (NADPH-d)-containing neurons in the brains of aged rats. The performance of aged rats (30 months old) in a radial arm maze task was significantly impaired compared to the performance of young rats (3 months old). The number of neurons containing NADPH-d reactivity in the cerebral cortex and striatum of aged rats was significantly reduced, by approximately 50 and 30 percent, respectively, compared to that in young rats. NO synthase activity in discrete brain regions of aged rats, i.e., in the cerebral cortex, striatum and hippocampus was not different from that in young rats, although the activity in the cerebellum of aged rats was significantly lower than that in young rats. These results suggest that the reduction in the number of NADPH-d-positive cells in the brains of aged rats may be involved in aging-associated learning impairment in rats.