One pot ‘click’ reactions: tandem enantioselective biocatalytic epoxide ring opening and [3+2] azide alkyne cycloaddition

Halohydrin dehalogenase (HheC) can perform enantioselective azidolysis of aromatic epoxides to 1,2-azido alcohols which are subsequently ligated to alkynes producing chiral hydroxy triazoles in a one-pot procedure with excellent enantiomeric excess.

Spin coherent quantum transport of electrons between defects in diamond

The nitrogen-vacancy color center in diamond has rapidly emerged as an important solid-state system for quantum information processing. While individual spin registers have been used to implement small-scale diamond quantum computing, the realization of a large-scale device requires development of an on-chip quantum bus for transporting information between distant qubits. Here we propose a method for coherent quantum transport of an electron and its spin state between distant NV centers. Transport is achieved by the implementation of spatial stimulated adiabatic Raman passage through the optical control of the NV center charge states and the confined conduction states of a diamond nanostructure. Our models show that for two NV centers in a diamond nanowire, high fidelity transport can be achieved over distances of order hundreds of nanometres in timescales of order hundreds of nanoseconds. Spatial adiabatic passage is therefore a promising option for realizing an on-chip spin quantum bus

Superconductivity in Co-doped LaFeAsO

Here we report the synthesis and basic characterization of LaFe1-xCoxAsO for several values of x. The parent phase LaFeAsO orders antiferromagnetically (TN ~ 145 K). Replacing Fe with Co is expected to both electron dope the system and introduce disorder in the FeAs layer. For x = 0.05 antiferromagnetic order is destroyed and superconductivity is observed at Tconset = 11.2 K. For x = 0.11 superconductivity is observed at Tc(onset) = 14.3 K, and for x = 0.15 Tc = 6.0 K. Superconductivity is not observed for x = 0.2 and 0.5, but for x = 1, the material appears to be ferromagnetic (Tc ~ 56 K) as judged by magnetization measurements. We conclude that Co is an effective dopant to induce superconductivity. Somewhat surprisingly, the system appears to tolerate considerable disorder in the FeAs planes.Comment: 19 pages, 9 figure

Neurons derived from human embryonic stem cells extend long-distance axonal projections through growth along host white matter tracts after intra-cerebral transplantation

Human pluripotent stem cells have the capacity for directed differentiation into a wide variety of neuronal subtypes that may be useful for brain repair. While a substantial body of research has lead to a detailed understanding of the ability of neurons in fetal tissue grafts to structurally and functionally integrate after intra-cerebral transplantation, we are only just beginning to understand the in vivo properties of neurons derived from human pluripotent stem cells. Here we have utilized the human embryonic stem (ES) cell line Envy, which constitutively expresses green fluorescent protein (GFP), in order to study the in vivo properties of neurons derived from human ES cells. Rapid and efficient neural induction, followed by differentiation as neurospheres resulted in a GFP+ neural precursor population with traits of neuroepithelial and dorsal forebrain identity. Ten weeks after transplantation into neonatal rats, GFP+ fiber patterns revealed extensive axonal growth in the host brain, particularly along host white matter tracts, although innervation of adjacent nuclei was limited. The grafts were composed of a mix of neural cell types including differentiated neurons and glia, but also dividing neural progenitors and migrating neuroblasts, indicating an incomplete state of maturation at 10 weeks. This was reflected in patch-clamp recordings showing stereotypical properties appropriate for mature functional neurons, including the ability to generate action potentials, as well profiles consistent for more immature neurons. These findings illustrate the intrinsic capacity for neurons derived from human ES cells to integrate at a structural and functional level following transplantation

Selection of Psyllid-Resistant Forage Varieties from an Inter-Specific Breeding Program of \u3cem\u3eLeucaena leucocephala\u3c/em\u3e with \u3cem\u3eL. pallida\u3c/em\u3e

Leucaena (Leucaena leucocephala) pastures for beef cattle production are productive and sustainable; however, susceptibility to the psyllid insect (Heteropsylla cubana) has limited expansion of current commercial cultivars into more humid areas (\u3e 800 mm/yr) (Shelton and Dalzell 2007). Psyllids can also cause intermittent damage in lower rainfall regions during humid periods. The psyllid, which arrived in Australia in 1986, is a leaf-sucking insect specific to the Leucaena genus, feeding on the growing tips of susceptible cultivars (Bray 1994). Psyllid damage can reduce production by as much as 50-70% in humid regions and 20-50% in subhumid environments (Bray 1994; Mullen and Shelton 2003). Work on psyllid resistance in the Leucaena genus through the 1990s showed that several Leucaena species, including the tetraploid L. pallida, had good levels of resistance (Mullen et al. 2003). A breeding program to develop psyllid-resistant varieties began in 2002 at The University of Queensland (UQ) based on the F1 inter-specific hybrids between L. leucocephala and L. pallida (known as ‘KX2’), developed at the University of Hawaii (Brewbaker 2008). Between 2002 and 2005, UQ initiated a program of recurrent selection in an attempt to produce stable outcrossed KX2-derived lines but inbreeding depression for yield and poor forage quality led to a change in the breeding strategy, and a backcrossing program was implemented between 2005 and 2008. Two cycles of backcrossing to elite L. leucocephala ssp. glabrata material were completed followed by 2 cycles of progeny testing and selection for self-compatibility to achieve stability and uniformity (2009 - 2012). Forty elite psyllid-resistant lines were then evaluated to identify the most suitable lines for release to industry. This paper describes the results of these trials

The role of Sirt7 and Sirt1 in adipocyte differentiation and maintenance of metabolic homeostasis

Sirtuins are NAD+-dependent protein deacetylases or ADP-ribosyltransferases, which play decisive roles in chromatin silencing, cell cycle regulation, cellular differentiation, metabolism, stress resistance and tumorigenesis. In mammals, sirtuins emerged as key metabolic sensors in various tissues and play a prominent role in metabolic adaptation to energy/nutrient stress. Sirt1 and Sirt6 are believed to act synergistically to prevent liver steatosis, especially under high-fat diet. Sirt1 and Sirt2 inhibit adipogenesis, and Sirt1 promotes the brown remodeling of white adipose tissue to control the metabolic balance in adipose tissue. Sirt7 was postulated to regulate rDNA transcription by associating with RNA polymerase I (Pol I) and maintain oncogenic transformation through deacetylation of histone H3K18, but the role of Sirt7 in metabolic regulation has remained enigmatic. Here, using the Sirt7 knockout mice and Sirt7 knock down approaches, my results describe the role of Sirt7 in maintenance of metabolic homeostasis in liver and the adipocytes differentiation in white adipose tissue. In liver, Sirt7 is required for the stimulation of hepatic rDNA transcription in response to insulin and is necessary for the fasting/refeeding adaptation. The second part of the study demonstrates the essential role of Sirt7 in adipocytes differentiation and white adipose tissue homeostasis. Absence of Sirt7 resulted in increased protein accumulation and activity of Sirt1 and restricted formation of white adipose tissue. In addition, my thesis shows that Sirt7 interacts with Sirt1 and restricts Sirt1 activity by inhibition of Sirt1 auto-deacetylation. These data uncover a new level of complexity in regulation of sirtuin activity and identify autocatalytic posttranscriptional modification as a new principle for regulation of Sirt1 activity. The antagonistic interactions between the two nuclear sirtuins are crucial to establish a well-balanced signalling network required for the maintenance of metabolic homeostasis. In the last part of this thesis, two Sirt1 targeting mouse strains were generated, which allow conditional, tissue specific inactivation of the Sirt1 gene and double knock out Sirt1 and Sirt7 in mice. These mouse models will help to further evaluate the sirtuin functions and the cross-regulatory network between Sirt1 and Sirt7 in the whole body or in the individual tissues.Sirtuine sind NAD+-abhängige Protein Deacetylasen und/oder ADP-Ribosyltransferasen, die entscheidende Rollen in einer Vielzahl von Prozessen spielen. Dazu gehören: Zellzyklusregulation, Differenzierung, metabolische Regulation, Stressresistenz sowie Tumorentstehung und Chromatin-Remodellierung. In Säugetieren nehmen Sirtuine eine Schlüsselrolle als metabolische Sensoren ein und regulieren die Adaptation auf Energie- und Nährstoffveränderungen. Synergistische Funktionen wurden für Sirt1 und Sirt6 in der Leber beschrieben. Beide Sirtuine wirken der Entwicklung von Lebersteatose, insbesondere bei fettreicher Ernährung, entgegen. Bei der Differenzierung von weißem Fettgewebe (Adipogenese) wurde eine hemmende Wirkung von Sirt1 und Sirt2 beobachtet. Des Weiteren, fördert Sirt1 die Entstehung von braunem Fettgewebe aus weißem Fett und kontrolliert somit die metabolische Balance im Fettgewebe. Für Sirt7 wurde bislang eine Funktion in der Regulation der rDNA Transkription durch die Interaktion mit der RNA-Polymerase I postuliert, eine Rolle in der Regulation metabolischer Prozesse konnte bis jetzt aber noch nicht nachgewiesen werden. In meiner Arbeit konnte ich mittels der Sirt7 Knock Out Maus bzw. verschiedener Sirt7 Knock Down Versuche belegen, dass Sirt7 eine Rolle in der Aufrechterhaltung der metabolischen Homöostase in der Leber und in der Differenzierung von Adipozyten in weißem Fettgewebe spielt. In der Leber ist Sirt7 für die Anregung der rDNA Transkription als Antwort auf eine Stimulation durch Insulin notwendig. Zudem konnte belegt werden, dass Sirt7 für eine Anpassung an Hungerphasen und anschließender Nahrungsaufnahme erforderlich ist. Im zweiten Teil meiner Arbeit konnte ich zeigen, dass die Funktion von Sirt7 in der Differenzierung von Adipozyten und in der Homöostase des weißen Fettgewebes essentiell ist. Hier resultiert der Verlust von Sirt7 in einer vermehrten Proteinakkumulation und einer erhöhten Aktivität von Sirt1, die der Fettgewebsentstehung entgegen wirkt. Hier konnte durch meine Arbeit eine Interaktion zwischen Sirt7 und Sirt1 belegt werden, welche mit einem Aktivitätsverlust von Sirt1 durch Inhibierung dessen Auto-Deacetylasefunktion einhergeht. Diese Ergebnisse decken eine neue Stufe der Komplexität der Aktivitätsanpassung der Sirtuine auf und identifizieren eine posttranskriptionelle Modifizierung als einen neuen Weg der Sirt1 Regulation durch dessen autokatalytische Aktivität. Die antagonistische Interaktion zwischen diesen zwei nukleären Sirtuinen ist entscheidend um eine ausgewogene Verknüpfung einzelner Signalwege herzustellen, die für die Aufrechterhaltung der metabolischen Homöostase notwendig sind. Im letzten Teil meiner Arbeit wurden zwei konditionelle Sirt1 Knock Out Mausstämme generiert, welche einerseits eine gewebsspezifische Inaktivierung von Sirt1 und zum anderen die gleichzeitige Ausschaltung von Sirt1 und Sirt7 in Mäusen erlauben. Die entstandenen Mausmodelle können helfen, die Funktionen von Sirt1 und Sirt7 und deren gegenseitige Beeinflussung im gesamten Organismus oder speziell in einzelnen Organen genauer zu untersuchen

The 6df galaxy survey: The near-infrared fundamental plane of early-type galaxies

We determine the near-infrared Fundamental Plane (FP) for ~10 4 early-type galaxies in the 6-degree Field Galaxy Survey (6dFGS). We fit the distribution of central velocity dispersion, near-infrared surface brightness and half-light radius with a 3D Gaussian model using a maximum-likelihood method. The model provides an excellent empirical fit to the observed FP distribution and the method proves robust and unbiased. Tests using simulations show that it gives superior results to regression techniques in the presence of significant and correlated uncertainties in all three parameters, censoring of the data by various selection effects and outliers in the data sample. For the 6dFGS J-band sample we find an FP with Re∝σ01.52±0.03Ie-0.89±0.01, similar to previous near-infrared determinations and consistent with the H- and K-band FPs once allowance is made for differences in mean colour. The overall scatter in R e about the FP is σ r = 29 per cent, and is the quadrature sum of an 18 per cent scatter due to observational errors and a 23 per cent intrinsic scatter. Because of the Gaussian distribution of galaxies in FP space, σ r is not the distance error, which we find to be σ d = 23 per cent. Using group richness and local density as measures of environment, and morphologies based on visual classifications, we find that the FP slopes do not vary with environment or morphology. However, for fixed velocity dispersion and surface brightness, field galaxies are on average 5 per cent larger than galaxies in groups or higher density environments, and the bulges of early-type spirals are on average 10 per cent larger than ellipticals and lenticulars. The residuals about the FP show significant trends with environment, morphology and stellar population. The strongest trend is with age, and we speculate that age is the most important systematic source of offsets from the FP, and may drive the other trends through its correlations with environment, morphology and metallicity. These results will inform our use of the near-infrared FP in deriving relative distances and peculiar velocities for 6dFGS galaxies

Peptide-Based Scaffolds Support Human Cortical Progenitor Graft Integration to Reduce Atrophy and Promote Functional Repair in a Model of Stroke

Stem cell transplants offer significant hope for brain repair following ischemic damage. Pre-clinical work suggests that therapeutic mechanisms may be multi-faceted, incorporating bone-fide circuit reconstruction by transplanted neurons, but also protection/regeneration of host circuitry. Here, we engineered hydrogel scaffolds to form "bio-bridges" within the necrotic lesion cavity, providing physical and trophic support to transplanted human embryonic stem cell-derived cortical progenitors, as well as residual host neurons. Scaffolds were fabricated by the self-assembly of peptides for a laminin-derived epitope (IKVAV), thereby mimicking the brain's major extracellular protein. Following focal ischemia in rats, scaffold-supported cell transplants induced progressive motor improvements over 9 months, compared to cell- or scaffold-only implants. These grafts were larger, exhibited greater neuronal differentiation, and showed enhanced electrophysiological properties reflective of mature, integrated neurons. Varying graft timing post-injury enabled us to attribute repair to both neuroprotection and circuit replacement. These findings highlight strategies to improve the efficiency of stem cell grafts for brain repair

Observations and comparisons of cloud microphysical properties in spring and summertime Arctic stratocumulus clouds during the ACCACIA campaign

Measurements from four case studies in spring and summer-time Arctic stratocumulus clouds during the Aerosol-Cloud Coupling And Climate Interactions in the Arctic (ACCACIA) campaign are presented. We compare microphysics observations between cases and with previous measurements made in the Arctic and Antarctic. During ACCACIA, stratocumulus clouds were observed to consist of liquid at cloud tops, often at distinct temperature inversions. The cloud top regions precipitated low concentrations of ice into the cloud below. During the spring cases median ice number concentrations (~ 0.5 L−1) were found to be lower by about a factor of 5 than observations from the summer campaign (~ 3 L−1). Cloud layers in the summer spanned a warmer temperature regime than in the spring and enhancement of ice concentrations in these cases was found to be due to secondary ice production through the Hallett–Mossop (H–M) process. Aerosol concentrations during spring ranged from ~ 300–400 cm−3 in one case to lower values of ~ 50–100 cm−3 in the other. The concentration of aerosol with sizes Dp > 0.5 μm was used in a primary ice nucleus (IN) prediction scheme (DeMott et al., 2010). Predicted IN values varied depending on aerosol measurement periods but were generally greater than maximum observed median values of ice crystal concentrations in the spring cases, and less than the observed ice concentrations in the summer due to the influence of secondary ice production. Comparison with recent cloud observations in the Antarctic summer (Grosvenor et al., 2012), reveals lower ice concentrations in Antarctic clouds in comparable seasons. An enhancement of ice crystal number concentrations (when compared with predicted IN numbers) was also found in Antarctic stratocumulus clouds spanning the H–M temperature zone; however, concentrations were about an order of magnitude lower than those observed in the Arctic summer cases but were similar to the peak values observed in the colder Arctic spring cases, where the H–M mechanism did not operate

Inflation Dynamics and Reheating

We review the theory of inflation with single and multiple fields paying particular attention to the dynamics of adiabatic and entropy/isocurvature perturbations which provide the primary means of testing inflationary models. We review the theory and phenomenology of reheating and preheating after inflation providing a unified discussion of both the gravitational and nongravitational features of multi-field inflation. In addition we cover inflation in theories with extra dimensions and models such as the curvaton scenario and modulated reheating which provide alternative ways of generating large-scale density perturbations. Finally we discuss the interesting observational implications that can result from adiabatic-isocurvature correlations and non-Gaussianity.Comment: 51 pages, latex, 16 figures, version to appear in Reviews of Modern Physic