First observation of 28O.

Subjecting a physical system to extreme conditions is one of the means often used to obtain a better understanding and deeper insight into its organization and structure. In the case of the atomic nucleus, one such approach is to investigate isotopes that have very different neutron-to-proton (N/Z) ratios than in stable nuclei. Light, neutron-rich isotopes exhibit the most asymmetric N/Z ratios and those lying beyond the limits of binding, which undergo spontaneous neutron emission and exist only as very short-lived resonances (about 10-21 s), provide the most stringent tests of modern nuclear-structure theories. Here we report on the first observation of 28O and 27O through their decay into 24O and four and three neutrons, respectively. The 28O nucleus is of particular interest as, with the Z = 8 and N = 20 magic numbers1,2, it is expected in the standard shell-model picture of nuclear structure to be one of a relatively small number of so-called 'doubly magic' nuclei. Both 27O and 28O were found to exist as narrow, low-lying resonances and their decay energies are compared here to the results of sophisticated theoretical modelling, including a large-scale shell-model calculation and a newly developed statistical approach. In both cases, the underlying nuclear interactions were derived from effective field theories of quantum chromodynamics. Finally, it is shown that the cross-section for the production of 28O from a 29F beam is consistent with it not exhibiting a closed N = 20 shell structure.

Probing the Symmetry Energy with the Spectral Pion Ratio.

Many neutron star properties, such as the proton fraction, reflect the symmetry energy contributions to the equation of state that dominate when neutron and proton densities differ strongly. To constrain these contributions at suprasaturation densities, we measure the spectra of charged pions produced by colliding rare isotope tin (Sn) beams with isotopically enriched Sn targets. Using ratios of the charged pion spectra measured at high transverse momenta, we deduce the slope of the symmetry energy to be 42

Extending the Southern Shore of the Island of Inversion to

Detailed spectroscopy of the neutron-unbound nucleus ^{28}F has been performed for the first time following proton/neutron removal from ^{29}Ne/^{29}F beams at energies around 230 MeV/nucleon. The invariant-mass spectra were reconstructed for both the ^{27}F^{(*)}+n and ^{26}F^{(*)}+2n coincidences and revealed a series of well-defined resonances. A near-threshold state was observed in both reactions and is identified as the ^{28}F ground state, with S_{n}(^{28}F)=-199(6) keV, while analysis of the 2n decay channel allowed a considerably improved S_{n}(^{27}F)=1620(60) keV to be deduced. Comparison with shell-model predictions and eikonal-model reaction calculations have allowed spin-parity assignments to be proposed for some of the lower-lying levels of ^{28}F. Importantly, in the case of the ground state, the reconstructed ^{27}F+n momentum distribution following neutron removal from ^{29}F indicates that it arises mainly from the 1p_{3/2} neutron intruder configuration. This demonstrates that the island of inversion around N=20 includes ^{28}F, and most probably ^{29}F, and suggests that ^{28}O is not doubly magic.

Fragmentation of Single-Particle Strength around the Doubly Magic Nucleus

Spectroscopic factors of neutron-hole and proton-hole states in ^{131}Sn and ^{131}In, respectively, were measured using one-nucleon removal reactions from doubly magic ^{132}Sn at relativistic energies. For ^{131}In, a 2910(50)-keV γ ray was observed for the first time and tentatively assigned to a decay from a 5/2^{-} state at 3275(50) keV to the known 1/2^{-} level at 365 keV. The spectroscopic factors determined for this new excited state and three other single-hole states provide first evidence for a strong fragmentation of single-hole strength in ^{131}Sn and ^{131}In. The experimental results are compared to theoretical calculations based on the relativistic particle-vibration coupling model and to experimental information for single-hole states in the stable doubly magic nucleus ^{208}Pb.

Ethical and medical management of a pregnant woman with brain stem death resulting in delivery of a healthy child and organ donation.

Maternal brain death during pregnancy remains an exceedingly complex situation that requires not only a well-considered medical management plan, but also careful decision-making in a legally and ethically delicate situation. Management of brain dead pregnant patients needs to adhere to special strategies that support the mother in a way that she can deliver a viable and healthy child. Brain death in pregnant women is very rare, with only a few published cases. We present a case of a pregnant woman with previously diagnosed multiple brain cavernomas that led to intracranial hemorrhage and brain stem death during the 21st week of pregnancy. The condition that can be proven unequivocally, using tests that do not endanger viability of the fetus, is brain stem death, diagnosed through absence of cranial reflexes. The patient was successfully treated until delivery of a healthy female child at 29weeks of gestation. The patient received continuous hormone substitution therapy, fetal monitoring and extrinsic regulation of maternal homeostasis over 64days. After delivery, the final diagnosis of brain death was established through multi-slice computerized tomography pan-angiography. This challenging case discusses ethical and medical circumstances arising from a diagnosis of maternal brain death, while showing that prolongation of somatic life support in a multidisciplinary setting can result in a successful pregnancy outcome.

17ß-Estradiol upregulates ecto-5'-nucleotidase (CD73) in hippocampal synaptosomes of female rats through action mediated by estrogen receptor-α and -ß.

17ß-Estradiol (E2) crucially affects several processes in the hippocampus of both sexes. E2 acts upon estradiol receptors ERα and ERß, influencing target gene expression and/or modulates intracellular signaling cascades. Another potent modulator of hippocampal function is nucleoside adenosine, the final product of ectonucleotidase cascade, enzymes which hydrolyze extracellular ATP to adenosine. The last and rate-limiting step of the hydrolysis is catalyzed by membrane-bound ecto-5'-nucleotidase (eN). Previous findings obtained on adenosine metabolism in brain suggest that eN may be modulated by ovarian steroids. Therefore, the present study reports that the activity and protein abundance of membrane-bound eN fluctuates across the estrus cycle in the hippocampal synaptosomes of female rats. Further, we analyzed the role of E2 and its intracellular receptors on the expression of eN in ovariectomized females. We found that E2 upregulated eN activity and protein abundance in the hippocampal synaptosomes. Application of nonspecific ER antagonist, ICI 182,780 and selective ERα and ERß agonists, PPT and DPN, respectively, demonstrated the involvement of both receptor subtypes in observed actions. Selective ERα receptor agonist, PPT, induced upregulation of both the protein level and activity of eN, while application of selective ERß receptor agonist, DPN, increased only the activity of eN. In both cases, E2 entered into the intracellular compartment and activated ER(s), which was demonstrated by membrane impermeable E2-BSA conjugate. Together these results imply that E2-induced effects on connectivity and functional properties of the hippocampal synapses may be in part mediated through observed effect on eN.

Effects of chronic cerebral hypoperfusion and low-dose progesterone treatment on apoptotic processes, expression and subcellular localization of key elements within Akt and Erk signaling pathways in rat hippocampus.

The present study attempted to investigate how chronic cerebral hypoperfusion (CCH) and repeated low-dose progesterone (P) treatment affect gene and protein expression, subcellular distribution of key apoptotic elements within protein kinase B (Akt) and extracellular signal-regulated kinases (Erk) signal transduction pathways, as well as neurodegenerative processes and behavior. The results revealed the absence of Erk activation in CCH in cytosolic and synaptosomal fractions, indicating a lower threshold of Akt activation in brain ischemia, while P increased their levels above control values. CCH induced an increase in caspase 3 (Casp 3) and poly (ADP-ribose) polymerase (PARP) gene and protein expression. However, P restored expression of examined molecules in all observed fractions, except for the levels of Casp 3 in synapses which highlighted its possible non-apoptotic or even protective function. Our study showed the absence of nuclear factor kappa-light-chain-enhancer of activated b cells (NF-κB) response to this type of ischemic condition and its strong activation under the influence of P. Further, the initial increase in the number of apoptotic cells and amount of DNA fragmentation induced by CCH was significantly reduced by P. Finally, P reversed the CCH-induced reduction in locomotor activity, while promoting a substantial decrease in anxiety-related behavior. Our findings support the concept that repeated low-dose post-ischemic P treatment reduces CCH-induced neurodegeneration in the hippocampus. Neuroprotection is initiated through the activation of investigated kinases and regulation of their downstream molecules in subcellular specific manner, indicating that this treatment may be a promising therapy for alleviation of CCH-induced pathologies.

Time course of cerebral hypoperfusion-induced neurodegenerative changes in the cortex of male and female rats.

To study time-dependent and gender-specific intracellular and biochemical mechanisms that lead to neurodegeneration due to moderate but persistent reduction of cerebral blood flow, adult male and female Wistar rats were divided into two main groups - controls that underwent sham operation and animals subjected to permanent bilateral occlusion of common carotid arteries. Animals were sacrificed 3, 7 or 90 days following the insult. Expression of several apoptotic proteins in synaptic fractions along with Fluoro-Jade B staining and DNA fragmentation assay were used to estimate the apoptotic processes and potential neurodegeneration in cerebral cortex. Data suggest a time-specific increase of Bax as well as time- and gender-associated downregulation in protein expression of Bcl-2, up-regulation of procaspase 3, accompanied with increased cleavage of procaspase 3 and PARP in synaptic terminals. Furthermore, time- but not gender-specific neurodegeneration was observed. Our findings support the concept of time- and gender-associated response to permanent bilateral occlusion of common carotid arteries, which would enable better understanding of the mechanisms underlying cerebral hypoperfusion.

Gasification of torrefied Miscanthus × giganteus in an air-blown bubbling fluidized bed gasifier.

Torrefaction is suggested to be an effective method to improve the fuel properties of biomass and gasification of torrefied biomass should provide a higher quality product gas than that from unprocessed biomass. In this study, both raw and torrefied Miscanthus × giganteus (M×G) were gasified in an air-blown bubbling fluidized bed (BFB) gasifier using olivine as the bed material. The effects of equivalence ratio (ER) (0.18-0.32) and bed temperature (660-850°C) on the gasification performance were investigated. The results obtained suggest the optimum gasification conditions for the torrefied M × G are ER 0.21 and 800°C. The product gas from these process conditions had a higher heating value (HHV) of 6.70 MJ/m(3), gas yield 2m(3)/kg biomass (H2 8.6%, CO 16.4% and CH4 4.4%) and cold gas efficiency 62.7%. The comparison between raw and torrefied M × G indicates that the torrefied M × G is more suitable BFB gasification.

Low-dose dexamethasone treatment promotes the pro-survival signalling pathway in the adult rat prefrontal cortex.

Synthetic glucocorticoid dexamethasone (DEX), a highly potent anti-inflammatory and immunosuppressive agent, is widely used in the treatment of brain cancer, as well as for inflammatory and autoimmune diseases. The present study aimed to determine whether low-dose subchronic DEX treatment (100 µg/kg for eight consecutive days) exerts long-term effects on apoptosis in the adult rat prefrontal cortex (PFC) by examining the expression of cell death-promoting molecules [poly(ADP-ribose) polymerase (PARP), p53, procaspase 3, cleaved caspase 3, Bax] and cell-survival molecules (AKT, Bcl-2). The results obtained revealed that body, thymus and adrenal gland weights, as well corticosterone levels, in the serum and PFC were reduced 1 day after the last DEX injection. In the PFC, DEX caused activation of AKT, augmentation of pro-survival Bcl-2 protein and an enhanced Bcl-2/Bax protein ratio, as well Bcl-2 translocation to the mitochondria. An unaltered profile with respect to the protein expression of apoptotic molecules PARP, procaspase 3 and Bax was detected, whereas p53 protein was decreased. Reverse transcriptase -polymerase chain reaction analysis showed a decrease of p53 mRNA levels and no significant difference in Bcl-2 and Bax mRNA expression in DEX-treated rats. Finally, a DNA fragmentation assay and Fluoro-Jade staining demonstrated no considerable changes in apoptosis in the rat PFC. Our findings support the concept that low-dose DEX creates a hypocorticoid state in the brain and also indicate that subchronic DEX treatment activates the pro-survival signalling pathway but does not change apoptotic markers in the rat PFC. This mechanism might be relevant for the DEX-induced apoptosis resistance observed during and after chemotherapy of patients with brain tumours.

17ß-estradiol modulates mitochondrial Ca²âº flux in rat caudate nucleus and brain stem.

The aim of this study was to examine the rapid non-genomic effect of 17ß-estradiol (E2) on Ca(2+) transport in mitochondria isolated from the nerve terminals (synaptosomes) of caudate nuclei (NC) and brain stems (BS) of ovariectomised female rats. In physiological conditions no effect of E2 on Ca(2+) influx into synaptosomal mitochondria through ruthenium red (RR)-sensitive uniporter was observed. However, in the presence of uncoupling agent carbonyl cyanide4-(trifluoromethoxy)phenylhydrazone (FCCP) (1µmol/l), pre-treatment with 0.5nmol/l E2 protected mitochondrial membrane potential and consequently increased Ca(2+) influx (2.3-fold in NC and 3.1-fold in BS). At the same time, 0.5nmol/l E2 by increasing the affinity of mitochondrial Na(+)/Ca(2+) exchanger for Na(+) inhibited mitochondrial Ca(2+) efflux in NC and BS by about 40%. Also, the specific binding of physiological E2 concentrations (0.1-10nmol/l) to isolated synaptosomal mitochondria was detected. Using membrane impermeable E2 bound to bovine serum albumin and selective inhibitor of mitochondrial Na(+)/Ca(2+) exchanger, we obtained that E2's action on mitochondrial Ca(2+) efflux at least partially is due to the direct effects on the mitochondrial membrane and/or Na(+)/Ca(2+) exchanger located in inner mitochondrial membrane. Our results implicate E2 as a modulator of Ca(2+) concentration in mitochondrial matrix, and ultimately in the cytosol. Given the vital role of Ca(2+) in regulation of total nerve cells activity, especially energy metabolism, neurotransmission and directing the cells toward survival or cell death, the effects on mitochondrial Ca(2+) transport could be one of the important modes of E2 neuromodulatory action independent of the genome.

Inhibition of mitochondrial Na+-dependent Ca²+ efflux by 17ß-estradiol in the rat hippocampus.

Our results, as well as those of others, have indicated that 17ß-estradiol (E2) exerts its nongenomic effects in neuronal cells by affecting plasma membrane Ca(2+) flux. In neuronal cells mitochondria possess Ca(2+) buffering properties as they both sequester and release Ca(2+). The goal of this study was to examine the rapid non-genomic effect of E2 on mitochondrial Ca(2+) transport in hippocampal synaptosomes from ovariectomised rats. In addition, we aimed to determine if, and to what extent, E2 receptors participated in mitochondrial Ca(2+) transport modulation by E2 in vitro. E2-specific binding and Ca(2+) transport was monitored. At physiological E2 concentrations (0.1-1.5 nmol/L), specific E2 binding to mitochondria isolated from hippocampal synaptosomes was detected with a B(max.) and K(m) of 37.6±2.6 fmol/mg protein and 0.69±0.14 nmol/L of free E2, respectively. The main mitochondrial Ca(2+) influx mechanism is the Ruthenium Red-sensitive uniporter driven by mitochondrial membrane potential. Despite no effect of E2 on Ca(2+) influx, a physiological E2 concentration (0.5 nmol/L) protected mitochondrial membrane potential and consequently Ca(2+) influx from the uncoupling agent carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (1 µmol/L). In neuronal cells the predominant mitochondrial Ca(2+) efflux mechanism is the Na(+)/Ca(2+) exchanger. E2 caused Ca(2+) efflux inhibition (by 46%) coupled with increased affinity of the Na(+)/Ca(2+) exchanger for Na(+). Using E2 receptor (ERα and ERß) antagonists and agonists, we confirmed ERß's involvement in E2-induced mitochondrial membrane potential protection as well as Ca(2+) efflux inhibition. In summary, our results indicate that the non-genomic neuromodulatory role of E2 in rat hippocampus is achieved by affecting mitochondrial Ca(2+) transport via, in part, mitochondrial ERß.

Combined high-resolution array-based comparative genomic hybridization and expression profiling of ETV6/RUNX1-positive acute lymphoblastic leukemias reveal a high incidence of cryptic Xq duplications and identify several putative target genes within the commonly gained region.

Seventeen ETV6/RUNX1-positive pediatric acute lymphoblastic leukemias were investigated by high-resolution array-based comparative genomic hybridization (array CGH), gene expression profiling and fluorescence in situ hybridization. Comparing the array CGH and gene expression patterns revealed that genomic imbalances conferred a great impact on the expression of genes in the affected regions. The array CGH analyses identified a high frequency of cytogenetically cryptic genetic changes, for example, del(9p) and del(12p). Interestingly, a duplication of Xq material, varying between 30 and 60 Mb in size, was found in 6 of 11 males (55%), but not in females. Genes on Xq were found to have a high expression level in cases with dup(Xq); a similar overexpression was confirmed in t(12;21)-positive cases in an external gene expression data set. By studying the expression profile and the proposed function of genes in the minimally gained region, several candidate target genes (SPANXB, HMGB3, FAM50A, HTATSF1 and RAP2C) were identified. Among them, the testis-specific SPANXB gene was the only one showing a high and uniform overexpression, irrespective of gender and presence of Xq duplication, suggesting that this gene plays an important pathogenetic role in t(12;21)-positive leukemia.

Dynamics of terrace formation in a nanostructured thin block copolymer film.

We have used dynamic self-consistent field (DSCF) theory to investigate the structural evolution of an ABA block copolymer thin film placed between a solid substrate and a free surface. In line with the few existing theoretical studies for pure homopolymers and mixtures, the free interface is introduced by a void component. In our calculations, the free surface experiences surface roughening and eventually the formation of terraces, as in the experiments. The kinetic pathway of the microstructures was compared to findings of an existing detailed experimental study (Knoll, A.; Lyakhova, K. S.; Horvat, A.; Krausch, G.; Sevink, G. J. A.; Zvelindovsky, A. V.; Magerle, R. Nat. Mater. 2004, 3, 886) and was found to be equivalent in detail. This corroborates our assumption in this earlier work that the pathway due to changing film thickness is similar to a pathway due to changing surface energetics. Moreover, our calculations show for the first time that microstructural transitions are a driving force of polymer/air interface curving and the formation of terraces.

Inhibition of rat brain ecto-atpase activity by various drugs.

The in vitro effect of digoxin, verapamil, propranolol, carbamazepine, diazepam and promethazine were investigated on the ecto-ATPase activity of synaptosomal plasma membranes from the rat brain. ATP hydrolyzing activities of the enzyme were not affected by digoxin while the use of all other drugs resulted in significant and dose-dependent ihibition in ATP hydrolysis. According to values of IC(50) and K(iapp), the order of inhibitory potency of the drugs applied was: diazepam > promethazine > verapamil > propranolol >> carbamazepine. Kinetic analysis of the nature of the ATPase inhibition revealed that it resulted from a direct action of drugs on the enzyme protein. The aim of the present study was to determine the potential neuromodulatory side effects of the drugs investigated. The results achieved indicated that all investigated drugs, except digoxin, may modulate neuronal activities via the purinergic receptors P2 by increasing extracellular concentrations of ATP as a consequence of inhibition of the ecto-ATPase activity. Our findings indicate that it may be useful to take into consideration the possible side effects of the investigated drugs, when they are used in treatment of different pathologies, particularly in the treatment of epilepsy by carbamazepine and diazepam.

Selective inhibition of brain Na,K-ATPase by drugs.

The effect of drugs from the class of cardiac (methyldigoxin, verapamil, propranolol), antiepileptic (carbamazepine), sedative (diazepam) and antihistaminic (promethazine) drugs on Na,K-ATPase activity of plasma membranes was studied in rat brain synaptosomes. Methyldigoxin in a concentration of 0.1 mmol/l inhibits enzyme activity by 80 %. Verapamil, propranolol and promethazine in concentrations of 20, 20 and 2 mmol/l respectively, entirely inhibit the ATPase activity. Carbamazepine and diazepam in concentrations of 0.02-60 mmol/l have no effect on the activity of this enzyme. According to the drug concentrations that inhibit 50 % of enzyme activity (IC(50)), the potency can be listed in the following order: methyldigoxin promethazine verapamil ? propranolol. From the inhibition of commercially available purified Na,K-ATPase isolated from porcine cerebral cortex in the presence of chosen drugs, as well as from kinetic studies on synaptosomal plasma membranes, it may be concluded that the drugs inhibit enzyme activity, partly by acting directly on the enzyme proteins. Propranolol, verapamil and promethazine inhibitions acted in an uncompetitive manner. The results suggest that these three drugs may contribute to neurological dysfunctions and indicate the necessity to take into consideration the side effects of the investigated drugs during the treatment of various pathological conditions.

Determination of pesticides in honey by ultrasonic solvent extraction and thin-layer chromatography.

A rapid method for quantitative determination of atrazine and simazine in honey samples was investigated. The procedure was based on the extraction of pesticides by sonication with benzene:water = 1:1 (v/v) mixture, thin-layer chromatographic separation and quantification by CAMAG Video Documentation system in conjunction with the Reprostar 3. The extraction procedure was optimized with regard to the amount of solvent, duration of sonication and the number of extraction steps. The apparent recovery of pesticides from honey was 92.3 +/- 2.4 for atrazine and 94.2 +/- 2.8 for simazine, when they were extracted in three steps for 20 min using 20 ml of solvent. Ultrasonic solvent extraction was compared with traditional shake-flask extraction method.

Developmental profile of NTPDase activity in synaptic plasma membranes isolated from rat cerebral cortex.

In the present study the developmental profile of ATP-hydrolyzing activity promoted by NTPDase 1, its kinetic properties and the enzyme protein abundance associated with synaptic plasma membrane from rat cerebral cortex were characterized. NTPDase 1 activity increased from birth to day 30; afterwards it decreased and remained unchanged from adulthood (90 days) to senescence (365 days). Kinetic analysis revealed that enzyme exhibited the highest specific activity at day 30 and highest apparent affinity for ATP at day 365; however, V(max)/K(m) values remained unchanged for each age studied. Immunoblot analysis demonstrated that relative abundance of NTPDase 1 is highest at day 15 during ontogeny. The discrepancy between maximum enzyme activity and maximum enzyme protein abundance indicates that NTPDase 1 may have an additional role during development.

Direct imaging and mesoscale modelling of phase transitions in a nanostructured fluid.

The kinetics of phase transitions is essential for understanding pattern formation in structured fluids. These fluids play a key role in the morphogenesis of biological cells, and they are very common in pharmaceutical products and plastic materials. Until now, it has not been possible to follow phase transitions in structured fluids experimentally in real time and with high spatial resolution. Previous work has relied on static images and indirect experimental evidence from spatially averaging scattering experiments. Simulating the processes with computer models is a further challenge because of the multiple time and length scales involved. Our movies based on in situ scanning force microscopy show the time sequence of the elementary steps of a phase transition in a fluid film of block copolymer from the cylinder to the perforated lamella phase. The movies validate a versatile simulation model that gives physical insight into the nature of the process. Our approach provides a means of improving the study and understanding of pattern formation processes in nanostructured fluids. We expect a significant impact on nanotechnology where block copolymers serve as self-organized templates for the synthesis of inorganic nanostructured materials.