Gyorshűtéssel, mechanikus ötvözéssel, illetve nagy deformációval előállított nanokristályos anyagok mikroszerkezete, termikus és mechanikai tulajdonságai = Microstructure, thermal and mechanical properties of nanocrystalline materials produced by rapid solidification, mechanical alloying or by severe plastic deformation

Tömbi amorf ötvözetekből kiindulva amorf és nanokristályos fázisokat tartalmazó heterogén rendszereket állítottunk elő. Az üvegesedési hőmérséklet közelében végzett deformációnál a viszkozitás reciproka lineárisan csökken a nanokristályos térfogathányaddal. Cu60Zr20Ti20 összetételű kristályos mintákban nagy nyomáson történő csavarással (HPT) részleges amorfizációt észleltünk. A mechanikai hatásra történő amorfizáció fordított folyamata a nagy deformáció hatására bekövetkező kristályosodás: amorf Cu60Zr20Ti20 minták HPT deformációjakor nanokristályos fázisok képződését figyeltük meg szinkrotron-XRD vizsgálatokkal . Al85Ce8Ni5Co2 amorf ötvözet HPT deformációjánál kimutattuk, hogy a termikus hatásokra képződő és a deformáció-keltette kristályos fázisok nem azonosak. Tiszta fémeken, valamint Al és Mg alapú ötvözeteken könyöksajtolással (ECAP) vizsgáltuk az extrém nagy alakítások hatását a mikroszerkezetre. Széles deformációs tartományban érvényes új empírikus feszültség-deformáció függvényt javasoltunk fcc fémekre, amely visszaadja az ismert Hollomon- és Voce-formulákat. Új kiértékelési eljárásokkal röntgen vonalprofil analízis alapján vizsgáltuk a rétegződési hibákat és az ikresedést, amelyek szerepet játszhatnak az inverz Hall-Petch viselkedésben. Szinkrotron mellet végzett röntgen-tomográfiával meghatároztuk alumínium-mátrixú kompozitok és fémhabok 3D mikroszerkezetét, ennek felhasználásával végeselem szimulációkat végeztünk a deformáció modellezésére. | Heterogeneous materials containing amorphous and nanocrystalline (nc) phases were produced from bulk metallic glasses. Upon deformation around the glass transition temperature the reciprocal viscosity decreases linearly with the nc volume fraction. In polycrystalline Cu60Zr20Ti20 samples partial amorphisation could be achieved by high pressure torsion (HPT). The inverse process, formation of nc phases during HPT was observed in rapidly solidified amorphous CuZrTi samples by synchrotron X-ray diffraction. HPT-induced crystallization was also detected in amorphous Al85Ce8Ni5Co2 where the nc products were different from those obtained by thermal crystallization. The effect of severe plastic deformation was studied by equal channel angular pressing on pure metals and on Al and Mg based alloys. A new empirical stress-strain formula, including as special cases the Hollomon- and Voce-equations, and valid in a wide range of strain, has been proposed for fcc metals. By a new evaluation method of X-ray diffraction peak profiles the role of stacking faults and twinning was investigated, since it has been suggested that these might influence the occurrence of the inverse Hall-Petch behavior. 3D microstructure of particle reinforced Al-matrix composites and foams has been determined by synchrotron X-ray tomography. On the basis of the real microstructure finite element modeling was used to reproduce the stress-strain curves

Determination of 17α-hydroxylase-C_17,20-lyase (P450_17α) enzyme activities and their inhibition by selected steroidal picolyl and picolinylidene compounds

17α-hydroxylase-C17,20-lyase (P45017α) is a key regulator enzyme of the steroid hormone biosynthesis in both the adrenals and the testes. Inhibition of this enzyme can block androgen synthesis in an early step, and may thereby be useful in the treatment of several androgen-dependent diseases. We developed radio-substrate in vitro incubation methods for the determination of the distinct 17α-hydroxylase and C17,20-lyase activities of the enzyme using rat testicular homogenate as enzyme source. With this method we have studied the inhibiting activity of selected steroidal picolyl and picolinylidene compounds. Tests revealed a substantial inhibitory action of the 17-picolinyliden-androst-4-en-3-one compound

Glycine transporter inhibitors

Interneurons operating with glycine neurotransmitter are involved in the regulation of pain transmission in the dorsal horn of the spinal cord. In addition to interneurons, glycine release also occurs from glial cells neighboring glutamatergic synapses in the spinal cord. Neuronal and glial release of glycine is controlled by glycine transporters (GlyTs). Inhibitors of the two isoforms of GlyTs, the astrocytic type-1 (GlyT-1) and the neuronal type-2 (GlyT-2), decrease pain sensation evoked by injuries of peripheral sensory neurons or inflammation. The function of dorsal horn glycinergic interneurons has been suggested to be reduced in neuropathic pain, which can be reversed by GlyT-2 inhibitors (Org-25543, ALX1393). Several lines of evidence also support that peripheral nerve damage or inflammation may shift glutamatergic neurochemical transmission from N-methyl-D aspartate (NMDA) NR1/NR2A receptor- to NR1/NR2B receptor-mediated events (subunit switch). This pathological overactivation of NR1/NR2B receptors can be reduced by GlyT-1 inhibitors (NFPS, Org-25935), which decrease excessive glycine release from astroglial cells or by selective antagonists of NR2B subunits (ifenprodil, Ro 25-6981). Although several experiments suggest that GlyT inhibitors may represent a novel strategy in the control of neuropathic pain, proving this concept in human beings is hampered by lack of clinically applicable GlyT inhibitors. We also suggest that drugs inhibiting both GlyT-1 and GlyT-2 non-selectively and reversibly, may favorably target neuropathic pain. In this paper we overview inhibitors of the two isoforms of GlyTs as well as the effects of these drugs in experimental models of neuropathic pain. In addition, the possible mechanisms of action of the GlyT inhibitors, i.e. how they affect the neurochemical and pain transmission in the spinal cord, are also discussed. The growing evidence for the possible therapeutic intervention of neuropathic pain by GlyT inhibitors further urges development of drugable compounds, which may beneficially restore impaired pain transmission in various neuropathic conditions

A Previously Uncharacterized Factor associated with Metabolism and Energy (FAME/C14orf105/CCDC198/1700011H14Rik) is related to Evolutionary Adaptation, Energy Balance, and Kidney Physiology

In this study we use comparative genomics to uncover a gene with uncharacterized function ( 1700011H14Rik/C14orf105/CCDC198 ), which we hereby name FAME (Factor Associated with Metabolism and Energy). We observe that FAME shows an unusually high evolutionary divergence in birds and mammals. Through the comparison of single nucleotide polymorphisms, we identify gene flow of FAME from Neandertals into modern humans. We conduct knockout experiments on animals and observe altered body weight and decreased energy expenditure in Fame knockout animals, corresponding to genome-wide association studies linking FAME with higher body mass index in humans. Gene expression and subcellular localization analyses reveal that FAME is a membrane-bound protein enriched in the kidneys. Although the gene knockout results in structurally normal kidneys, we detect higher albumin in urine and lowered ferritin in the blood. Through experimental validation, we confirm interactions between FAME and ferritin and show co-localization in vesicular and plasma membranes

Chronic treatment with rofecoxib but not ischemic preconditioning of the myocardium ameliorates early intestinal damage following cardiac ischemia/reperfusion injury in rats

There is some recent evidence that cardiac ischemia/reperfusion (I/R) injury induces intestinal damage within days, which contributes to adverse cardiovascular outcomes after myocardial infarction. However, it is not clear whether remote gut injury has any detectable early signs, and whether different interventions aiming to reduce cardiac damage are also effective at protecting the intestine. Previously, we found that chronic treatment with rofecoxib, a selective inhibitor of cyclooxygenase-2 (COX-2), limited myocardial infarct size to a comparable extent as cardiac ischemic preconditioning (IPC) in rats subjected to 30-min coronary artery occlusion and 120-min reperfusion. In the present study, we aimed to analyse the early intestinal alterations caused by cardiac I/R injury, with or without the above-mentioned infart size-limiting interventions. We found that cardiac I/R injury induced histological changes in the small intestine within 2 h, which were accompanied by elevated tissue level of COX-2 and showed positive correlation with the activity of matrix metalloproteinase-2 (MMP-2), but not of MMP-9 in the plasma. All these changes were prevented by rofecoxib treatment. By contrast, cardiac IPC failed to reduce intestinal injury and plasma MMP-2 activity, although it prevented the transient reduction in jejunal blood flow in response to cardiac I/R. Our results demonstrate for the first time that rapid development of intestinal damage follows cardiac I/R, and that two similarly effective infarct size-limiting interventions, rofecoxib treatment and cardiac IPC, have different impacts on cardiac I/R-induced gut injury. Furthermore, intestinal damage correlates with plasma MMP-2 activity, which may be a biomarker for its early diagnosis

Lack of Small Intestinal Dysbiosis Following Long-Term Selective Inhibition of Cyclooxygenase-2 by Rofecoxib in the Rat

Intestinal dysbiosis is linked to numerous gastrointestinal disorders, including inflammatory bowel diseases. It is a question of debate if coxibs, selective inhibitors of cyclooxygenase (COX)-2, cause dysbiosis. Therefore, in the present study, we aimed to determine the effect of long-term (four weeks) selective inhibition of COX-2 on the small intestinal microbiota in the rat. In order to avoid mucosal damage due to topical effects and inflammation-driven microbial alterations, rofecoxib, a nonacidic compound, was used. The direct inhibitory effect of rofecoxib on the growth of bacteria was ruled out in vitro. The mucosa-sparing effect of rofecoxib was confirmed by macroscopic and histological analysis, as well as by measuring the intestinal levels of cytokines and tight junction proteins. Deep sequencing of bacterial 16S rRNA revealed that chronic rofecoxib treatment had no significant influence on the composition and diversity of jejunal microbiota. In conclusion, this is the first demonstration that long-term selective inhibition of COX-2 by rofecoxib does not cause small intestinal dysbiosis in rats. Moreover, inhibition of COX-2 activity is not likely to be responsible per se for microbial alterations caused by some coxibs, but other drug-specific properties may contribute to it

Search for flavor-changing neutral current interactions of the top quark and the Higgs boson decaying to a bottom quark-antiquark pair at root s=13 TeV

A search for flavor-changing neutral current interactions of the top quark (t) and the Higgs boson (H) is presented. The search is based on a data sample corresponding to an integrated luminosity of 137 fb(-1) recorded by the CMS experiment at the LHC in proton-proton collisions at root s = 13TeV. Events containing exactly one lepton (muon or electron) and at least three jets, among which at least two are identified as originating from the hadronization of a bottom quark, are analyzed. A set of deep neural networks is used for kinematic event reconstruction, while boosted decision trees distinguish the signal from the background events. No significant excess over the background predictions is observed, and upper limits on the signal production cross sections are extracted. These limits are interpreted in terms of top quark decay branching fractions (B) to the Higgs boson and an up (u) or a charm quark (c). Assuming one nonvanishing extra coupling at a time, the observed (expected) upper limits at 95% confidence level are B(t -> Hu) Hc) < 0.094 (0.086)%