Composite super-moiré lattices in double-aligned graphene heterostructures.

When two-dimensional (2D) atomic crystals are brought into close proximity to form a van der Waals heterostructure, neighbouring crystals may influence each other's properties. Of particular interest is when the two crystals closely match and a moiré pattern forms, resulting in modified electronic and excitonic spectra, crystal reconstruction, and more. Thus, moiré patterns are a viable tool for controlling the properties of 2D materials. However, the difference in periodicity of the two crystals limits the reconstruction and, thus, is a barrier to the low-energy regime. Here, we present a route to spectrum reconstruction at all energies. By using graphene which is aligned to two hexagonal boron nitride layers, one can make electrons scatter in the differential moiré pattern which results in spectral changes at arbitrarily low energies. Further, we demonstrate that the strength of this potential relies crucially on the atomic reconstruction of graphene within the differential moiré super cell.

Scanning gate microscopy of magnetic focusing in graphene devices: quantum versus classical simulation.

We compare classical versus quantum electron transport in recently investigated magnetic focusing devices (Bhandari et al 2016 Nano Lett. 16 1690) exposed to the perturbing potential of a scanning gate microscope (SGM). Using the Landauer-Büttiker formalism for a multi-terminal device, we calculate resistance maps that are obtained as the SGM tip is scanned over the sample. There are three unique regimes in which the scanning tip can operate (focusing, repelling, and mixed regime) which are investigated. Tip interacts mostly with electrons with cyclotron trajectories passing directly underneath it, leaving a trail of modified current density behind it. Other (indirect) trajectories become relevant when the tip is placed near the edges of the sample, and current is scattered between the tip and the edge. We point out that, in contrast to SGM experiments on gapped semiconductors, the STM tip can induce a pn junction in graphene, which improves contrast and resolution in SGM. We also discuss possible explanations for spatial asymmetry of experimentally measured resistance maps, and connect it with specific configurations of the measuring probes.

Strained graphene Hall bar.

The effects of strain, induced by a Gaussian bump, on the magnetic field dependent transport properties of a graphene Hall bar are investigated. The numerical simulations are performed using both classical and quantum mechanical transport theory and we found that both approaches exhibit similar characteristic features. The effects of the Gaussian bump are manifested by a decrease of the bend resistance, R B, around zero-magnetic field and the occurrence of side-peaks in R B. These features are explained as a consequence of bump-assisted scattering of electrons towards different terminals of the Hall bar. Using these features we are able to give an estimate of the size of the bump. Additional oscillations in R B are found in the quantum description that are due to the population/depopulation of Landau levels. The bump has a minor influence on the Hall resistance even for very high values of the pseudo-magnetic field. When the bump is placed outside the center of the Hall bar valley polarized electrons can be collected in the leads.

Characterization of the size and position of electron-hole puddles at a graphene p-n junction.

The effect of an electron-hole puddle on the electrical transport when governed by snake states in a bipolar graphene structure is investigated. Using numerical simulations we show that information on the size and position of the electron-hole puddle can be obtained using the dependence of the conductance on magnetic field and electron density of the gated region. The presence of the scatterer disrupts snake state transport which alters the conduction pattern. We obtain a simple analytical formula that connects the position of the electron-hole puddle with features observed in the conductance. The size of the electron-hole puddle is estimated from the magnetic field and gate potential that maximizes the effect of the puddle on the electrical transport.

Optimal dose of an anesthetic in epidural anesthesia and its effect on labor duration and administration of vacuum extractor and forceps.

This study examined the factors that influence the optimal dose of epidural anesthesia (EA), its effect on labor duration, and the frequency of vacuum and forceps administration at the end of delivery. The study group included 100 women who underwent vaginal delivery with EA with administration of 0.125% bupivacaine. A control group included 100 vaginally delivered women, without EA administration. In both groups delivery was stimulated by syntocinon. The level of labor pain influenced the optimal bolus dose of EA more than the body mass. However, the maintenance dose was influenced by both of these factors equally. Labor in the study group was somewhat shorter. In the group with EA the percentage of forceps and vacuum extractor application was twice that in the control group. There was no difference in average value of 5-minute Apgar scor in newborns.

Hydrogen peroxide affects contractile activity and anti-oxidant enzymes in rat uterus.

BACKGROUND AND PURPOSE: The effects of hydrogen peroxide (H(2)O(2)) on uterine smooth muscle are not well studied. We have investigated the effect and the mechanism of action of exogenous hydrogen peroxide on rat uteri contractile activity [spontaneous and calcium ion (Ca(2+))-induced] and the effect of such treatment on anti-oxidative enzyme activities. EXPERIMENTAL APPROACH: Uteri were isolated from virgin Wistar rats and suspended in an organ bath. Uteri were allowed to contract spontaneously or in the presence of Ca(2+) (6 mM) and treated with H(2)O(2) (2 microM-3 mM) over 2 h. Anti-oxidative enzyme activities (manganese superoxide dismutase-MnSOD, copper-zinc superoxide dismutase-CuZnSOD, catalase-CAT, glutathione peroxidase-GSHPx and glutathione reductase-GR) in H(2)O(2)-treated uteri were compared with those in uteri immediately frozen after isolation or undergoing spontaneous or Ca(2+)-induced contractions, without treatment with H(2)O(2). The effect of inhibitors (propranolol, methylene blue, L-NAME, tetraethylamonium, glibenclamide and 4-aminopyridine) on H(2)O(2)-mediated relaxation was explored. KEY RESULTS: H(2)O(2) caused concentration-dependent relaxation of both spontaneous and Ca(2+)-induced uterine contractions. After H(2)O(2) treatment, GSHPx and MnSOD activities were increased, while CuZnSOD and GR (In Ca(2+)-induced rat uteri) were decreased. N(omega)-nitro-L-arginine methyl ester antagonized the effect of H(2)O(2) on Ca(2+)-induced contractions. H(2)O(2)-induced relaxation was not affected by propranolol, potentiated by methylene blue and antagonized by tetraethylamonium, 4-aminopyridine and glibenclamide, with the last compound being the least effective. CONCLUSIONS AND IMPLICATIONS: H(2)O(2) induced dose-dependent relaxation of isolated rat uteri mainly via changes in voltage-dependent potassium channels. Decreasing generation of reactive oxygen species by stimulation of anti-oxidative pathways may lead to new approaches to the management of dysfunctional uteri.

Hydrogen storage properties of MgH2-diatomite composites obtained by high-energy ball milling.

To investigate the effects of specific porous microstructure of diatomite on the hydrogen storage properties of MgH(2), a two-step preparation was carried out. The first step was decrepitation of MgH(2) particle size during 10 h of milling. The second step was additional 1 h of milling with diatomite. The microstructure and phase composition of materials was characterized by X-ray diffraction, whereas the powder morphology and degree of additive dispersion were analyzed by scanning electron microscopy. The hydrogen desorption behaviour of nanocomposites was investigated by differential scanning calorimetry. The results show that addition of porous diatomite structure leads to decrease in desorption temperature, since there was no other effect that can have an influence on kinetics, such as formation of the metastable gamma-phase, reduction of oxides to the native metal and/or homogeneous dispersion of the catalyst. This indicates that the microstructure of added material plays the main role in the enhancement of desorption properties of composites.

Sodium nitroprusside regulates the relaxation of the longitudinal muscle in the gut.

Nitric oxide (NO) has been shown to mediate nonadrenergic-noncholinergic relaxation in gastrointestinal (GI) smooth muscle cells. As GI smooth muscles relaxations are partly dependent on NO, we decided to investigate the effect of sodium nitroprusside (SNP) on the longitudinal muscle contraction of the isolated guinea pig ileum. Increasing concentrations of SNP (10(-10)M, 10(-9)M, 10(-8)M, 10(-7)M, 10(-6)M and 10(-5)M) reduced ileum contractions stimulated by electrical stimulation (ES) (8-76%; p < 0.05) and by acetylcholine (Ach) (23-62%; p < 0.05) significantly and in a concentration-dependent manner. Furthermore, treatment with an inhibitor of the soluble guanylate cyclase, methylene blue (10 mM), antagonized significantly the relaxing effect of SNP (0-39%; p < 0.05, p < 0.01, p < 0.001 for ES- and 4-27%; p < 0.05 for Ach-induced contractions). The results show that treatment with 1 microM manganese-containing superoxide dismutase (MnSOD) and 10 microM L-arginine (L-arg) caused a significant decrease in SNP induced relaxations (6-55%; p < 0.05, p < 0.001 and 2-46%; p < 0.05, p < 0.01 for ES- and 15-28%; p < 0.05, p < 0.01, p < 0.001 and 12-32%; p < 0.05, p < 0.01 for Ach-induced contractions, respectively). In conclusion, our data suggest that SNP, which releases NO, is able to depress longitudinal muscle contraction of the isolated guinea pig ileum, suggesting that exogenous application of NO inhibits intestinal contractions of smooth muscle cells and that cGMP mediates the response to NO. In addition, MnSOD and L-arg decreased the relaxing effect of SNP on the isolated ileum of the guinea pig.

Effect of L-arginine on the relaxation caused by sodium nitroprusside on isolated rat renal artery.

In the present study we investigated the mechanism of nitric oxide induced relaxation of renal arteries, with or without endothelium, taken from normotensive and spontaneously hypertensive (SH) rats. With this purpose in mind, the effects of the nitric oxide donor, sodium nitroprusside (SNP), with and without L-arg in the medium, on isolated rat renal artery relaxation were studied. Relaxing effect of SNP was higher in normotensive (10(-5) M of SNP caused 220% of relaxation in the cases with endothelium and 240% without endothelium), in comparison with SH rats (100% of relaxation with endothelium and 150% without). L-arg antagonized the relaxing effect of SNP in the examined renal arteries, more in normotensive (100-160% with endothelium and 110-195% without) than in hypertensive ones (0-10% with endothelium and 35-75% without) at SNP concentrations 10(-7) - 10(-5) M, respectively (*P < 0.05; **P < 0.001). L-arg did not significantly change relaxing effect of SNP in the isolated renal arteries with endothelium taken from SH rats, which show that L-arg, by modifying the chemical versatility of NO into redox active forms -nitrosonium (NO+) and -nitroxyl (NO-), produces different relaxing effects in normotensive and hypertensive isolated arteries of rats, with or without endothelium, potentiating the role of nitroxyl induced relaxation in SH rats.

The anti-oxidative defence system in the isolated rat uterus during spontaneous rhythmic activity.

Possible interactions between nitric oxide donors, reactive oxygen species and anti-oxidative defence enzymes led us to determine the activities of anti-oxidative defence enzymes in isolated uterine smooth muscle before and after spontaneous rhythmic activity ex vivo. For our experiments we used isolated uteri from female Wistar rats. Our results showed an increase in total superoxide dismutase (SOD) and Mn SOD activities in uterine smooth muscle after spontaneous contractions when compared with nonexercised uterine smooth muscle. The activity of catalase (CAT) and glutathione preoxidase (GSH-Px) were also increased. No statistically significant changes in the activities of glutathione reductase (GR) and CuZn SOD were found. It is known that an organism's anti-oxidative defence system (guarding against excessive reactive oxygen species generation) requires balanced increments in its individual anti-oxidative enzyme activities rather than increases in the activity of only some enzymes without increases in others. Thus, we may conclude that some adaptive responses are found in exercised uterine smooth muscle but are not complete. Therefore, our results indicate that changes in anti-oxidative enzyme activities may influence the results of the examination of substances ex vivo.

The efficacy of selenium, WR-2721, and their combination in the prevention of adriamycin-induced cardiotoxicity in rats.

It is known that the antineoplastic drug adriamycin (ADR) can cause cardiotoxic effects. Some data imply that pretreatment with selenium (Se) and the radio- and chemoprotector, amifostine (WR-2721), may confer a protective effect. The aim of this study was to evaluate the efficacy of single doses of Se and WR-2721, alone or in combination, in the prevention of acute ADR-induced cardiotoxicity in male Wistar rats. Se, in the form of sodium selenite (1.6 mg/kg i.p.), and WR-2721 (300 mg/kg i.p.) were given 24 hours and 20 minutes, respectively, before ADR (6 mg/kg i.v.). The cardiotoxicity of ADR was recorded 48 hours after its administration because earlier studies revealed that structural damage of the myocardium occurs within this period. Evaluation of these toxic effects, as well as of the cardioprotective efficacy of the administered drugs, was performed using (1) ECG-records before and during the infusion of the proarrhythmogenic compound, aconitine (8 microg/kg/min i.v.) and (2) the serum activity of creatine kinase (CK), aspartate aminotransferase-(AST), lactate dehydrogenase (LDH), and its isoenzyme alpha-hydroxybutyrate dehydrogenase (alpha-HBDH). The results showed that the arrhythmogenic dose of aconitine was significantly reduced in ADR-treated rats (57.22 vs. 99.65 microg/kg in control; p < 0.05) and that this proarrhythmogenic compound caused a significant increase in heart rate in such animals compared to controls. Pretreatment with Se, WR-2721, and their combination partly reversed the arrhythmogenic dose of aconitine to control (72.09, 82.1, and 88.99 microg/kg, respectively). Se failed to prevent an aconitine-induced increase in heart rate, whereas WR-2721 and their combination successfully counteracted this effect. In addition, ADR produced a significant increase in the serum activity of all monitored enzymes. Pretreatment with Se failed to prevent this increase, whereas pretreatment with WR-2721 did. The best result was obtained with their combination. We conclude that the radio- and chemoprotector, WR-2721, particularly in combination with Se, may provide a significant protective effect against acute ADR-induced cardiotoxicity in rats.

T-2 toxin affects proliferation of three different neoplastic cell lines.

The antiproliferative effect of T-2 toxin (T-2) towards mouse melanoma B16 cells, human myelogenous leukemia K562 cells, and human cervix carcinoma, HeLa cells, was studied. For the first four days of T-2 presence B16 cell survival was decreased in dose dependent fashion. However, cell survival after eleven days T-2 action may be dual: some stimulation of cell growth that was direct function of the number of seeded cells per well was observed and cell survival (for the highest number of seeded cells) six times greater than control, was noticed at 20 nM T-2 toxin concentration. A smaller cell growth stimulation (cell survival more than 3 times higher than control) was observed with a lower cell number seeded per well. Nevertheless, by eleventh day concentrations of T-2 higher than 35 nM completely inhibited B16 cell proliferation. The same trend was noticed for T-2 action towards K562 cells. Treatment of HeLa cells with various T-2 concentrations led to a marked inhibition of cell survival that was more pronounced at the end of 44th or 72nd hour, than after the 20th hour of agent's action. ICs50 values obtained in the present work, suggest that B16 cells were the most sensitive to T-2 antiproliferative action, while HeLa cells were the most resistant. When PBMC were cultured with HeLa cells the antagonism against various T-2 concentrations was observed; cell survival determined after 44, or 72 hours of cells incubation, was less decreased compared to cultures treated with T-2, or with PBMC only. In addition, it was shown that T-2 and cis-DDP had an antagonist effect on HeLa cells survival.

[The effect of gammaphos on the course and outcome of surgical treatment in combined radiation injuries in pigs]. / Uticaj gamafosa na tok i ishod hirurskog lecenja udruzene radijacione povrede u svinja.

The effect of gamaphos (0.6 mmol kg-1 im, 20 min before irradiation) was investigated upon the course and outcome of the surgical management of combined radiation-gunshot injury in pigs. The hypothesis was tested that the infliction of perforating gunshot injury (LD0/30 days) in pigs in the latent phase of the acute radiation injury (LD0/30 days) results in the increase of the lethal outcome. Gamaphos treatment prevented the lethal outcome. Besides, wound reepithelization and granular tissue vascularization in protected pigs was more intensive in comparison with the unprotected ones.

Inhibitory effects of antagonists of bombesin/gastrin releasing peptide (GRP) and somatostatin analog (RC-160) on growth of HT-29 human colon cancers in nude mice.

Nude mice bearing xenografts of HT-29 human colon cancer cell line were treated for 4 weeks with somatostatin analog (RC-160), bombesin/gastrin releasing peptide (GRP) antagonists (RC-3095 and RC-3440). In three separate experiments somatostatin analog RC-160 (50 micrograms/day) released from microgranules significantly reduced tumor growth. Bombesin/GRP antagonists, RC-3095 and RC-3440 injected subcutaneously (s.c.) twice daily at a dose of 10 micrograms had the greatest and consistently significant inhibitory effect on tumor growth. RC-3095 given once daily s.c. at a dose of 20 micrograms was less effective. RC-3095 also inhibited metastatic tumor growth after intrasplenic injection of HT-29 cells in nude mice. Specific binding sites of somatostatin, bombesin and epidermal growth factor (EGF) were detected on intact HT-29 cells or on the membranes from HT-29 tumor xenografts. The inhibitory effects of bombesin antagonists on tumor growth were consistently linked with a significant down-regulation of EGF receptors. Bombesin/GRP antagonists and somatostatin analogs could be considered for the development of new hormonal therapies for colon cancer.

Peritubular Na-K exchange ion pump in maleate-treated frog kidney proximal tubular cells.

1. After perfusion of isolated frog kidneys for 1 hr with 10(-3) or 10(-2) M maleate Ringer, the peritubular membrane potential gradually declined in a dose-dependent manner. 2. The ouabain-like effects of maleate on cell Na and K activities were dose-dependent and smaller than the effects of zero K or 10(-4) M ouabain. Intracellular pH was not altered in the presence of 10(-2) M maleate. 3. The driving force for Na entry into the cell was reduced, respectively, to 81.4 and 58.4% (of control) in the presence of 10(-3) and 10(-2) M maleate. 4. There was no histochemically detectable inhibition of proximal tubule Na-K ATPase activity during 3 hr of perfusion with 10(-2) M maleate.

Expression of multiple water channel activities in Xenopus oocytes injected with mRNA from rat kidney.

To test the hypothesis that renal tissue contains multiple distinct water channels, mRNA prepared from either cortex, medulla, or papilla of rat kidney was injected into Xenopus oocytes. The osmotic water permeability (Pf) of oocytes injected with either 50 nl of water or 50 nl of renal mRNA (1 microgram/microliter) was measured 4 d after the injection. Pf was calculated from the rate of volume increase on exposure to hyposmotic medium. Injection of each renal mRNA preparation increased the oocyte Pf. This expressed water permeability was inhibited by p-chloromercuriphenylsulfonate and had a low energy of activation, consistent with the expression of water channels. The coinjection of an antisense oligonucleotide for CHIP28 protein, at an assumed > 100-fold molar excess, with either cortex, medulla, or papilla mRNA reduced the expression of the water permeability by approximately 70, 100, and 30%, respectively. Exposure of the oocyte to cAMP for 1 h resulted in a further increase in Pf only in oocytes injected with medulla mRNA. This cAMP activation was not altered by the CHIP28 antisense oligonucleotide. These results suggest that multiple distinct water channels were expressed in oocytes injected with mRNA obtained from sections of rat kidney: (a) CHIP28 water channels in cortex and medulla, (b) cAMP-activated water channels in medulla, and (c) cAMP-insensitive water channels in papilla.

Somatostatin analogue RC-160 and LH-RH antagonist SB-75 inhibit growth of MIA PaCa-2 human pancreatic cancer xenografts in nude mice.

Nude mice bearing xenografts of the MIA PaCa-2 human pancreatic cancer cell line were treated with sustained-release formulations (microcapsules) of luteinizing hormone releasing hormone (LH-RH) agonist [D-Trp6]-LH-RH, somatostatin analogue RC-160 (D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2), or combination of both analogues. Other groups of mice received daily subcutaneous injections of LH-RH antagonist SB-75 [Ac-D-Nal(2)',D- Phe(4Cl)2,D-Pal(3)3,D-Cit6,D-Ala10-LH-RH] or bombesin antagonist RC-3095. At necropsy, in mice given microcapsules releasing 25 micrograms/day of [D-Trp6]-LH-RH, tumor weight and volume were decreased, but not significantly, as compared with control mice. Microcapsules of RC-160, releasing 25 micrograms/day, significantly reduced tumor volume, percentage change in tumor volume, and tumor weight. Combination of RC-160 and [D-Trp6]-LH-RH inhibited tumor growth to a somewhat greater extent than RC-160 alone. Bombesin antagonist RC-3095, at a dose of 25 micrograms/day, did not influence the growth of tumors. In mice receiving 100 micrograms/day of antagonist SB-75, there was a significant decrease in tumor weight and volume and a significant reduction in the weight of ovaries and uteri. Specific binding of [125I]RC-160 and [125I][D-Trp6]-LH-RH, but not [125I]Tyr4-bombesin, was found on MIA PaCa-2 cells in culture. [D-Trp6]-LH-RH, SB-75, and RC-160 inhibited the growth of MIA PaCa-2 cells in vitro. Neither bombesin nor RC-3095 influenced the growth of MIA PaCa-2 cells in cultures. The results indicate that the LH-RH antagonist SB-75 could be tried for treatment of pancreatic cancer. Our findings confirm the efficacy of somatostatin analogue RC-160 in inhibiting the growth of pancreatic cancers and suggest that the combination of RC-160 and agonist [D-Trp6]-LH-RH might possibly increase the therapeutic response.

Effect of treatment with LHRH analogs containing cytotoxic radicals on the binding characteristics of receptors for luteinizing-hormone-releasing hormone in MXT mouse mammary carcinoma.

Binding capacities and apparent dissociation constants of receptors for luteinizing-hormone-releasing hormone (LHRH) were investigated in estrogen-independent MXT mammary cancers of untreated mice and after in vivo treatment with agonistic or antagonistic analogs of LHRH containing cytotoxic radicals: AJ-04 (agonist [D-Lys6]LHRH linked to methotrexate), T-98-([D-Lys6]LHRH coupled to glutaryl-2-(hydroxmethyl)anthraquinone (G-HMAQ)) and T-121/B (LHRH antagonist T-147 containing two residues of G-HMAQ), which induced tumor growth inhibition. The effects were compared to LHRH agonist [D-Trp6]LHRH and carriers [D-Lys6]LHRH, LHRH antagonist T-147, as well as to methotrexate, G-HMAQ and surgical bilateral overiectomy. Analysis of the binding data revealed that in control tumors the interaction of 125I-[D-TRP6]LHRH was consistent with the presence of one class of saturable, specific, noncooperative, high-affinity and low-capacity binding sites. Chronic treatment of mice bearing MXT tumors with LHRH analogs AJ-04 and T-121/B carrying cytotoxic radicals, but not with T-98 produced significant down-regulation of membrane receptors for LHRH. The largest decrease in dissociation binding constant and Bmax of receptors for LHRH was also found in animals treated with T-121/B. Specific, high affinity binding of 125I-labelled epidermal growth factor (EGF) was detected in the membranes from control and treated MXT tumors. Treatment with cytotoxic LHRH analogs, AJ-04, T-98 and especially with T-121/B, reduced maximal binding capacity of EGF receptors. Our results indicate that LHRH analogs carrying cytotoxic radicals retain their hormonal activity and inhibit tumor growth while inducing down-regulation of LHRH receptors. In addition, probably both components of the cytotoxic LHRH analog, peptide carriers and cytotoxic radicals, reduce the binding capacity of EGF receptors, which might be useful in the treatment of breast cancer.

Short-chain analogs of luteinizing hormone-releasing hormone containing cytotoxic moieties.

Five hexapeptide and heptapeptide analogs of luteinizing hormone-releasing hormone (LH-RH) were synthesized for use as carriers for cytotoxic compounds. These short analogs were expected to enhance target selectivity of the antineoplastic agents linked to them. Native LH-RH-(3-9) and LH-RH-(4-9) containing D-lysine and D-ornithine at position 6 were amidated with ethylamine and acylated on the N terminus. The receptor-binding affinity of one hexapeptide carrier AJ-41 (Ac-Ser-Tyr-D-Lys-Leu-Arg-Pro-NH-Et) to human breast cancer cell membranes was similar to that of [D-Trp6]LH-RH. Alkylating nitrogen mustards (melphalan, Ac-melphalan), anthraquinone derivatives including anticancer antibiotic doxorubicin, antimetabolite (methotrexate), and cisplatin-like platinum complex were linked to these peptides through their omega-amino group at position 6. The hybrid molecules showed no LH-RH agonistic activity in vitro and in vivo but had nontypical antagonistic effects on pituitary cells in vitro at the doses tested. These analogs showed a wide range of receptor-binding affinities to rat pituitaries and cell membranes of human breast cancer and rat Dunning prostate cancer. Several of these conjugates exerted some cytotoxic effects on MCF-7 breast cancer cell line.