Novel Synthesis and High Pressure Behavior of Na0.3CoO2 x 1.3 H2O and Related Phases

We have prepared powder samples of NaxCoO2 x yH2O using a new synthesis route. Superconductivity was observed in Na0.3CoO2 x 1.3H2O between 4 and 5K as indicated by the magnetic susceptibility. The bulk compressibilities of Na0.3CoO2 x 1.3H2O, Na0.3CoO2 x 0.6H2O and Na0.3CoO2 were determined using a diamond anvil cell and synchrotron powder diffraction. Chemical changes occurring under pressure when using different pressure transmitting media are discussed and further transport measurements are advocated.Comment: 7 pages, 4 figures, PRrapid submitte

Kink–antikink stripe interactions in the two-dimensional sine–Gordon equation

The main focus of the present work is to study quasi-one-dimensional kink–antikink stripes embedded in the two-dimensional sine–Gordon equation. Using variational techniques, we reduce the interaction dynamics between a kink and an antikink stripe on their respective time and space dependent widths and locations. The resulting reduced system of coupled equations is found to accurately describe the width and undulation dynamics of a single kink stripe as well as that of two interacting ones. As an aside, we also discuss two related topics: the computational identification of the kink center and its numerical implications and alternative perturbative and multiple scales approaches to the transverse direction induced dynamics for a single kink stripe in the two-dimensional realm

The Structure of a Rigorously Conserved RNA Element within the SARS Virus Genome

We have solved the three-dimensional crystal structure of the stem-loop II motif (s2m) RNA element of the SARS virus genome to 2.7-Å resolution. SARS and related coronaviruses and astroviruses all possess a motif at the 3′ end of their RNA genomes, called the s2m, whose pathogenic importance is inferred from its rigorous sequence conservation in an otherwise rapidly mutable RNA genome. We find that this extreme conservation is clearly explained by the requirement to form a highly structured RNA whose unique tertiary structure includes a sharp 90° kink of the helix axis and several novel longer-range tertiary interactions. The tertiary base interactions create a tunnel that runs perpendicular to the main helical axis whose interior is negatively charged and binds two magnesium ions. These unusual features likely form interaction surfaces with conserved host cell components or other reactive sites required for virus function. Based on its conservation in viral pathogen genomes and its absence in the human genome, we suggest that these unusual structural features in the s2m RNA element are attractive targets for the design of anti-viral therapeutic agents. Structural genomics has sought to deduce protein function based on three-dimensional homology. Here we have extended this approach to RNA by proposing potential functions for a rigorously conserved set of RNA tertiary structural interactions that occur within the SARS RNA genome itself. Based on tertiary structural comparisons, we propose the s2m RNA binds one or more proteins possessing an oligomer-binding-like fold, and we suggest a possible mechanism for SARS viral RNA hijacking of host protein synthesis, both based upon observed s2m RNA macromolecular mimicry of a relevant ribosomal RNA fold

HighP–TNano-Mechanics of Polycrystalline Nickel

We have conducted highP–Tsynchrotron X-ray and time-of-flight neutron diffraction experiments as well as indentation measurements to study equation of state, constitutive properties, and hardness of nanocrystalline and bulk nickel. Our lattice volume–pressure data present a clear evidence of elastic softening in nanocrystalline Ni as compared with the bulk nickel. We show that the enhanced overall compressibility of nanocrystalline Ni is a consequence of the higher compressibility of the surface shell of Ni nanocrystals, which supports the results of molecular dynamics simulation and a generalized model of a nanocrystal with expanded surface layer. The analytical methods we developed based on the peak-profile of diffraction data allow us to identify “micro/local” yield due to high stress concentration at the grain-to-grain contacts and “macro/bulk” yield due to deviatoric stress over the entire sample. The graphic approach of our strain/stress analyses can also reveal the corresponding yield strength, grain crushing/growth, work hardening/softening, and thermal relaxation under highP–Tconditions, as well as the intrinsic residual/surface strains in the polycrystalline bulks. From micro-indentation measurements, we found that a low-temperature annealing (T < 0.4 Tm) hardens nanocrystalline Ni, leading to an inverse Hall–Petch relationship. We explain this abnormal Hall–Petch effect in terms of impurity segregation to the grain boundaries of the nanocrystalline Ni

Resveratrol Targeting of Carcinogen-Induced Brain Endothelial Cell Inflammation Biomarkers MMP-9 and COX-2 is Sirt1-Independent

The occurrence of a functional relationship between the release of metalloproteinases (MMPs) and the expression of cyclooxygenase (COX)-2, two inducible pro-inflammatory biomarkers with important pro-angiogenic effects, has recently been inferred. While brain endothelial cells play an essential role as structural and functional components of the blood-brain barrier (BBB), increased BBB breakdown is thought to be linked to neuroinflammation. Chemopreventive mechanisms targeting both MMPs and COX-2 however remain poorly investigated. In this study, we evaluated the pharmacological targeting of Sirt1 by the diet-derived and antiinflammatory polyphenol resveratrol. Total RNA, cell lysates, and conditioned culture media from human brain microvascular endothelial cells (HBMEC) were analyzed using qRT-PCR, immunoblotting, and zymography respectively. Tissue scan microarray analysis of grade I–IV brain tumours cDNA revealed increased gene expression of Sirt-1 from grade I–III but surprisingly not in grade IV brain tumours. HBMEC were treated with a combination of resveratrol and phorbol 12-myristate 13-acetate (PMA), a carcinogen known to increase MMP-9 and COX-2 through NF-κB. We found that resveratrol efficiently reversed the PMA-induced MMP-9 secretion and COX-2 expression. Gene silencing of Sirt1, a critical modulator of angiogenesis and putative target of resveratrol, did not lead to significant reversal of MMP-9 and COX-2 inhibition. Decreased resveratrol inhibitory potential of carcinogen-induced IκB phosphorylation in siSirt1-transfected HBMEC was however observed. Our results suggest that resveratrol may prevent BBB disruption during neuroinflammation by inhibiting MMP-9 and COX-2 and act as a pharmacological NF-κB signal transduction inhibitor independent of Sirt1

Designing a broad-spectrum integrative approach for cancer prevention and treatment

Targeted therapies and the consequent adoption of "personalized" oncology have achieved notablesuccesses in some cancers; however, significant problems remain with this approach. Many targetedtherapies are highly toxic, costs are extremely high, and most patients experience relapse after a fewdisease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistantimmortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are notreliant upon the same mechanisms as those which have been targeted). To address these limitations, aninternational task force of 180 scientists was assembled to explore the concept of a low-toxicity "broad-spectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspectsof relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a widerange of high-priority targets (74 in total) that could be modified to improve patient outcomes. For thesetargets, corresponding low-toxicity therapeutic approaches were then suggested, many of which werephytochemicals. Proposed actions on each target and all of the approaches were further reviewed forknown effects on other hallmark areas and the tumor microenvironment. Potential contrary or procar-cinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixedevidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of therelationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. Thisnovel approach has potential to be relatively inexpensive, it should help us address stages and types ofcancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for futureresearch is offered

Medulloblastoma has a global impact on health related quality of life: Findings from an international cohort

Background: Understanding the global impact of medulloblastoma on health related quality of life (HRQL) is critical to characterizing the broad impact of this disease and realizing the benefits of modern treatments. We evaluated HRQL in an international cohort of pediatric medulloblastoma patients. Methods: Seventy-six patients were selected from 10 sites across North America, Europe, and Asia, who participated in the Medulloblastoma Advanced Genomics International Consortium (MAGIC). The Health Utilities Index (HUI) was administered to patients and/or parents at each site. Responses were used to determine overall HRQL and attributes (ie specific subdomains). The impact of various demographic and medical variables on HRQL was considered—including molecular subgroup. Results: The majority of patients reported having moderate or severe overall burden of morbidity for both the HUI2 and HUI3 (HUI2 = 60%; HUI3 = 72.1%) when proxy-assessed. Self-care in the HUI2 was rated as higher (ie better outcome) for patients from Western versus Eastern sites, P =.02. Patients with nonmetastatic status had higher values (ie better outcomes) for the HUI3 hearing, HUI3 pain, and HUI2 pain, all P <.05. Patients treated with a gross total resection also had better outcomes for the HUI3 hearin