Imaging Oxygen Defects and their Motion at a Manganite Surface

Manganites are technologically important materials, used widely as solid oxide fuel cell cathodes: they have also been shown to exhibit electroresistance. Oxygen bulk diffusion and surface exchange processes are critical for catalytic action, and numerous studies of manganites have linked electroresistance to electrochemical oxygen migration. Direct imaging of individual oxygen defects is needed to underpin understanding of these important processes. It is not currently possible to collect the required images in the bulk, but scanning tunnelling microscopy could provide such data for surfaces. Here we show the first atomic resolution images of oxygen defects at a manganite surface. Our experiments also reveal defect dynamics, including oxygen adatom migration, vacancy-adatom recombination and adatom bistability. Beyond providing an experimental basis for testing models describing the microscopics of oxygen migration at transition metal oxide interfaces, our work resolves the long-standing puzzle of why scanning tunnelling microscopy is more challenging for layered manganites than for cuprates.Comment: 7 figure

Ultrafast spin dynamics and critical behavior in half-metallic ferromagnet : Sr_2FeMoO_6

Ultrafast spin dynamics in ferromagnetic half-metallic compound Sr_2FeMoO_6 is investigated by pump-probe measurements of magneto-optical Kerr effect. Half-metallic nature of this material gives rise to anomalous thermal insulation between spins and electrons, and allows us to pursue the spin dynamics from a few to several hundred picoseconds after the optical excitation. The optically detected magnetization dynamics clearly shows the crossover from microscopic photoinduced demagnetization to macroscopic critical behavior with universal power law divergence of relaxation time for wide dynamical critical region.Comment: 14 pages, 4 figures. Abstract and Figures 1 & 3 are correcte

Saturated Ferromagnetism and Magnetization Deficit in Optimally Annealed (Ga,Mn)As Epilayers

We examine the Mn concentration dependence of the electronic and magnetic properties of optimally annealed Ga1-xMnxAs epilayers for 1.35% < x < 8.3%. The Curie temperature (Tc), conductivity, and exchange energy increase with Mn concentration up to x ~ 0.05, but are almost constant for larger x, with Tc ~ 110 K. The ferromagnetic moment per Mn ion decreases monotonically with increasing x, implying that an increasing fraction of the Mn spins do not participate in the ferromagnetism. By contrast, the derived domain wall thickness, an important parameter for device design, remains surprisingly constant.Comment: 8 pages, 4 figures, submitted for Rapid Communication in Phys Rev

Characterization of a c-Rel inhibitor that mediates anticancer properties in hematologic malignancies by blocking NF-&#954;B-controlled oxidative stress responses

NF-\u3baB plays a variety of roles in oncogenesis and immunity that may be beneficial for therapeutic targeting, but strategies to selectively inhibit NF-\u3baB to exert antitumor activity have been elusive. Here, we describe IT-901, a bioactive naphthalenethiobarbiturate derivative that potently inhibits the NF-\u3baB subunit c-Rel. IT-901 suppressed graft-versus-host disease while preserving graft-versus-lymphoma activity during allogeneic transplantation. Further preclinical assessment of IT-901 for the treatment of human B-cell lymphoma revealed antitumor properties in vitro and in vivo without restriction to NF-\u3baB-dependent lymphoma. This nondiscriminatory, antilymphoma effect was attributed to modulation of the redox homeostasis in lymphoma cells resulting in oxidative stress. Moreover, NF-\u3baB inhibition by IT-901 resulted in reduced stimulation of the oxidative stress response gene heme oxygenase-1, and we demonstrated that NF-\u3baB inhibition exacerbated oxidative stress induction to inhibit growth of lymphoma cells. Notably, IT-901 did not elicit increased levels of reactive oxygen species in normal leukocytes, illustrating its cancer selective properties. Taken together, our results provide mechanistic insight and preclinical proof of concept for IT-901 as a novel therapeutic agent to treat human lymphoid tumors and ameliorate graft-versus-host disease

The impact of predation by marine mammals on Patagonian toothfish longline fisheries

Predatory interaction of marine mammals with longline fisheries is observed globally, leading to partial or complete loss of the catch and in some parts of the world to considerable financial loss. Depredation can also create additional unrecorded fishing mortality of a stock and has the potential to introduce bias to stock assessments. Here we aim to characterise depredation in the Patagonian toothfish (Dissostichus eleginoides) fishery around South Georgia focusing on the spatio-temporal component of these interactions. Antarctic fur seals (Arctocephalus gazella), sperm whales (Physeter macrocephalus), and orcas (Orcinus orca) frequently feed on fish hooked on longlines around South Georgia. A third of longlines encounter sperm whales, but loss of catch due to sperm whales is insignificant when compared to that due to orcas, which interact with only 5% of longlines but can take more than half of the catch in some cases. Orca depredation around South Georgia is spatially limited and focused in areas of putative migration routes, and the impact is compounded as a result of the fishery also concentrating in those areas at those times. Understanding the seasonal behaviour of orcas and the spatial and temporal distribution of “depredation hot spots” can reduce marine mammal interactions, will improve assessment and management of the stock and contribute to increased operational efficiency of the fishery. Such information is valuable in the effort to resolve the human-mammal conflict for resources

Adults with corrected oesophageal atresia: is oesophageal function associated with complaints and/or quality of life?

The aim of this study was to evaluate oesophageal function after correction of oesophageal atresia in adults, and to investigate the association between complaints, oesophageal function and quality of life (QoL). Twenty-five adults were included who participated in previous follow-up studies, during which complaints of dysphagia and gastro-oesophageal reflux (GOR), results of upper gastrointestinal endoscopy, oesophageal biopsies and QoL had been collected. Manometry was performed in 20 patients, 24 h pH-measurements were performed in 21 patients. pH-values (sample time 5 s) were calculated using criteria of Johnson and DeMeester. Associations were tested with ANOVA and χ2-tests. Ten patients (48%) reported complaints of dysphagia, seven (33%) of GOR. The amplitude of oesophageal contractions was low (<15 mmHg) in four patients (20%). pH-measurements showed pathological reflux in three patients (14%). Patients reporting dysphagia more often had disturbed motility (P = 0.011), and lower scores on the domains “general health perceptions” (SF-36) (P = 0.026), “standardised physical component” (SF-36) (P = 0.013), and “physical well-being” (GIQLI) (0.047). No other associations were found. This study shows a high percentage of oesophageal motility disturbances and a moderate percentage of GOR after correction of oesophageal atresia. Patients reporting dysphagia, whom more often had disturbed motility, seemed to be affected by these symptoms in their QoL

Cascade oxime formation, cyclization to a nitrone, and intermolecular dipolar cycloaddition.

Simple haloaldehydes, including enolisable aldehydes, were found to be suitable for the formation of cyclic products by cascade (domino) condensation, cyclisation, dipolar cycloaddition chemistry. This multi-component reaction approach to heterocyclic compounds was explored by using hydroxylamine, a selection of aldehydes, and a selection of activated dipolarophiles. Initial condensation gives intermediate oximes that undergo cyclisation with displacement of halide to give intermediate nitrones; these nitrones undergo in situ intermolecular dipolar cycloaddition reactions to give isoxazolidines. The cycloadducts from using dimethyl fumarate were treated with zinc/acetic acid to give lactam products and this provides an easy way to prepare pyrrolizinones, indolizinones, and pyrrolo[2,1-a]isoquinolinones. The chemistry is illustrated with a very short synthesis of the pyrrolizidine alkaloid macronecine and a formal synthesis of petasinecine

Nap1 regulates proper CENP-B binding to nucleosomes

CENP-B is a widely conserved centromeric satellite DNA-binding protein, which specifically binds to a 17-bp DNA sequence known as the CENP-B box. CENP-B functions positively in the de novo assembly of centromeric nucleosomes, containing the centromere-specific histone H3 variant, CENP-A. At the same time, CENP-B also prevents undesired assembly of the CENP-A nucleosome through heterochromatin formation on satellite DNA integrated into ectopic sites. Therefore, improper CENP-B binding to chromosomes could be harmful. However, no CENP-B eviction mechanism has yet been reported. In the present study, we found that human Nap1, an acidic histone chaperone, inhibited the non-specific binding of CENP-B to nucleosomes and apparently stimulated CENP-B binding to its cognate CENP-B box DNA in nucleosomes. In human cells, the CENP-B eviction activity of Nap1 was confirmed in model experiments, in which the CENP-B binding to a human artificial chromosome or an ectopic chromosome locus bearing CENP-B boxes was significantly decreased when Nap1 was tethered near the CENP-B box sequence. In contrast, another acidic histone chaperone, sNASP, did not promote CENP-B eviction in vitro and in vivo and did not stimulate specific CENP-B binding to CENP-A nucleosomes in vitro. We therefore propose a novel mechanism of CENP-B regulation by Nap1

Natural and Synthetic Polymers as Inhibitors of Drug Efflux Pumps

Inhibition of efflux pumps is an emerging approach in cancer therapy and drug delivery. Since it has been discovered that polymeric pharmaceutical excipients such as Tweens® or Pluronics® can inhibit efflux pumps, various other polymers have been investigated regarding their potential efflux pump inhibitory activity. Among them are polysaccharides, polyethylene glycols and derivatives, amphiphilic block copolymers, dendrimers and thiolated polymers. In the current review article, natural and synthetic polymers that are capable of inhibiting efflux pumps as well as their application in cancer therapy and drug delivery are discussed