Reduction of leukocyte microvascular adherence and preservation of blood-brain barrier function by superoxide-lowering therapies in a piglet model of neonatal asphyxia

Background: Asphyxia is the most common cause of brain damage in newborns. Substantial evidence indicates that leukocyte recruitment in the cerebral vasculature during asphyxia contributes to this damage. We tested the hypothesis that superoxide radical (O2⋅_) promotes an acute post-asphyxial inflammatory response and blood-brain barrier (BBB) breakdown. We investigated the effects of removing O2⋅_ by superoxide dismutase (SOD) or C3, the cell-permeable SOD mimetic, in protecting against asphyxia-related leukocyte recruitment. We also tested the hypothesis that xanthine oxidase activity is one source of this radical.Methods: Anesthetized piglets were tracheostomized, ventilated, and equipped with closed cranial windows for the assessment of post-asphyxial rhodamine 6G-labeled leukocyte-endothelial adherence and microvascular permeability to sodium fluorescein in cortical venules. Asphyxia was induced by discontinuing ventilation. SOD and C3 were administered by cortical superfusion. The xanthine oxidase inhibitor oxypurinol was administered intravenously.Results: Leukocyte-venular adherence significantly increased during the initial 2 h of post-asphyxial reperfusion. BBB permeability was also elevated relative to non-asphyxial controls. Inhibition of O2⋅_ production by oxypurinol, or elimination of O2⋅_ by SOD or C3, significantly reduced rhodamine 6G-labeled leukocyte-endothelial adherence and improved BBB integrity, as measured by sodium fluorescein leak from cerebral microvessels.Conclusion: Using three different strategies to either prevent formation or enhance elimination of O2⋅_ during the post-asphyxial period, we saw both reduced leukocyte adherence and preserved BBB function with treatment. These findings suggest that agents which lower O2⋅_ in brain may be attractive new therapeutic interventions for the protection of the neonatal brain following asphyxia

Spontaneous Interlayer Charge Transfer near the Magnetic Quantum Limit

Experiments reveal that a confined electron system with two equally-populated layers at zero magnetic field can spontaneously break this symmetry through an interlayer charge transfer near the magnetic quantum limit. New fractional quantum Hall states at unusual total filling factors such as \nu = 11/15 (= 1/3 + 2/5) stabilize as signatures that the system deforms itself, at substantial electrostatic energy cost, in order to gain crucial correlation energy by "locking in" separate incompressible liquid phases at unequal fillings in the two layers (e.g., layered 1/3 and 2/5 states in the case of \nu = 11/15).Comment: 4 pages, 4 figures (1 color) included in text. Related papers at http://www.ee.princeton.edu/~hari/papers.htm

Exchange Instabilities in Semiconductor Double Quantum Well Systems

We consider various exchange-driven electronic instabilities in semiconductor double-layer systems in the absence of any external magnetic field. We establish that there is no exchange-driven bilayer to monolayer charge transfer instability in the double-layer systems. We show that, within the unrestricted Hartree-Fock approximation, the low density stable phase (even in the absence of any interlayer tunneling) is a quantum ``pseudospin rotated'' spontaneous interlayer phase coherent spin-polarized symmetric state rather than the classical Ising-like charge-transfer phase. The U(1) symmetry of the double quantum well system is broken spontaneously at this low density quantum phase transition, and the layer density develops quantum fluctuations even in the absence of any interlayer tunneling. The phase diagram for the double quantum well system is calculated in the carrier density--layer separation space, and the possibility of experimentally observing various quantum phases is discussed. The situation in the presence of an external electric field is investigated in some detail using the spin-polarized-local-density-approximation-based self-consistent technique and good agreement with existing experimental results is obtained.Comment: 24 pages, figures included. Also available at http://www-cmg.physics.umd.edu/~lzheng/preprint/ct.uu/ . Revised final version to appear in PR

Sheared Flow As A Stabilizing Mechanism In Astrophysical Jets

It has been hypothesized that the sustained narrowness observed in the asymptotic cylindrical region of bipolar outflows from Young Stellar Objects (YSO) indicates that these jets are magnetically collimated. The j cross B force observed in z-pinch plasmas is a possible explanation for these observations. However, z-pinch plasmas are subject to current driven instabilities (CDI). The interest in using z-pinches for controlled nuclear fusion has lead to an extensive theory of the stability of magnetically confined plasmas. Analytical, numerical, and experimental evidence from this field suggest that sheared flow in magnetized plasmas can reduce the growth rates of the sausage and kink instabilities. Here we propose the hypothesis that sheared helical flow can exert a similar stabilizing influence on CDI in YSO jets.Comment: 13 pages, 2 figure

Book Review of Serendipity: An Ecologist’s Quest to Understand Nature

A common thought among graduate students is: “how do established scientists get where they are today?” In Serendipity: An Ecologist’s Quest to Understand Nature, James Estes offers a personal reflection on research experiences spanning his 50-year career, beginning as a Ph.D. student in 1970 and concluding with recognition as a member of the National Academy of Sciences in 2014. Estes chronologically outlines the foundational trophic cascade ecology research that he and colleagues conducted in the Aleutian Islands, examining key relationships among kelp forests, sea otters, sea urchins, and killer whales through anecdotal stories of achievement and challenge. Estes’ 3 main goals in writing this book are to: (1) recount what he had learned from 50 years of research; (2) provide a larger story of how predators and prey interact with one another; and (3) explain how science “really happens.

Excitation of spiral density waves by convection in accretion discs

Motivated by the recent results of \citet{Lesur_Ogilvie10} on the transport properties of incompressible convection in protoplanetary discs, in this paper we study the role of compressibility and hence of another basic mode -- spiral density waves -- in convective instability in discs. We analyse the linear dynamics of non-axisymmetric convection and spiral density waves in a Keplerian disc with superadiabatic vertical stratification using the local shearing box approach. It is demonstrated that the shear associated with Keplerian differential rotation introduces a novel phenomenon, it causes these two perturbation modes to become coupled: during evolution the convective mode generates (trailing) spiral density waves and can therefore be regarded as a new source of spiral density waves in discs. The wave generation process studied here owes its existence solely to shear of the disc's differential rotation, and is a special manifestation of a more general linear mode coupling phenomena universally taking place in flows with an inhomogeneous velocity profile. We quantify the efficiency of spiral density wave generation by convection as a function of azimuthal and vertical wavenumbers of these modes and find that it is maximal and most powerful when both these length-scales are comparable to the disc scale height. We also show that unlike the convective mode, which tends to transport angular momentum inwards in the linear regime, the spiral density waves transport angular momentum outwards. Based on these findings, we suggest that in the non-linear regime spiral density waves generated by convection may play a role in enhancing the transport of angular momentum due the convective mode alone, which is actually being changed to outward by non-linearity, as indicated by above-mentioned recent developments.Comment: 17 pages, 8 figures, accepted for publication in MNRA

2-D models of layered protoplanetary discs: I. The ring instability

In this work we use the radiation hydrodynamic code TRAMP to perform a two-dimensional axially symmetric model of the layered disc. Using this model we follow the accumulation of mass in the dead zone due to the radially varying accretion rate. We found a new type of instability which causes the dead zone to split into rings. This "ring instability" works due to the positive feedback between the thickness of the dead zone and the mass accumulation rate. We give an analytical description of this instability, taking into account non-zero thickness of the dead zone and deviations from the Keplerian rotational velocity. The analytical model agrees reasonably well with results of numerical simulations. Finally, we speculate about the possible role of the ring instability in protoplanetary discs and in the formation of planets.Comment: 9 pages, 5 figures, accepted for publication in MNRA

A Review of Volatile Organic Compound Contamination in Post-Industrial Urban Centers: Reproductive Health Implications Using a Detroit Lens

Volatile organic compounds (VOCs) are a group of aromatic or chlorinated organic chemicals commonly found in manufactured products that have high vapor pressure, and thus vaporize readily at room temperature. While airshed VOCs are well studied and have provided insights into public health issues, we suggest that belowground VOCs and the related vapor intrusion process could be equally or even more relevant to public health. The persistence, movement, remediation, and human health implications of subsurface VOCs in urban landscapes remain relatively understudied despite evidence of widespread contamination. This review explores the state of the science of subsurface movement and remediation of VOCs through groundwater and soils, the linkages between these poorly understood contaminant exposure pathways and health outcomes based on research in various animal models, and describes the role of these contaminants in human health, focusing on birth outcomes, notably low birth weight and preterm birth. Finally, this review provides recommendations for future research to address knowledge gaps that are essential for not only tackling health disparities and environmental injustice in post-industrial cities, but also protecting and preserving critical freshwater resources

Progressive, Transgenerational Changes in Offspring Phenotype and Epigenotype following Nutritional Transition

Induction of altered phenotypes during development in response to environmental input involves epigenetic changes. Phenotypic traits can be passed between generations by a variety of mechanisms, including direct transmission of epigenetic states or by induction of epigenetic marks de novo in each generation. To distinguish between these possibilities we measured epigenetic marks over four generations in rats exposed to a sustained environmental challenge. Dietary energy was increased by 25% at conception in F0 female rats and maintained at this level to generation F3. F0 dams showed higher pregnancy weight gain, but lower weight gain and food intake during lactation than F1 and F2 dams. On gestational day 8, fasting plasma glucose concentration was higher and β-hydroxybutyrate lower in F0 and F1 dams than F2 dams. This was accompanied by decreased phosphoenolpyruvate carboxykinase (PEPCK) and increased PPARα and carnitine palmitoyl transferase-1 mRNA expression. PEPCK mRNA expression was inversely related to the methylation of specific CpG dinucleotides in its promoter. DNA methyltransferase (Dnmt) 3a2, but not Dnmt1 or Dnmt3b, expression increased and methylation of its promoter decreased from F1 to F3 generations. These data suggest that the regulation of energy metabolism during pregnancy and lactation within a generation is influenced by the maternal phenotype in the preceding generation and the environment during the current pregnancy. The transgenerational effects on phenotype were associated with altered DNA methylation of specific genes in a manner consistent with induction de novo of epigenetic marks in each generation