True scale-invariant random spatial networks.

Some aspects of real-world road networks seem to have an approximate scale invariance property, motivating study of mathematical models of random networks whose distributions are exactly invariant under Euclidean scaling. This requires working in the continuum plane, so making a precise definition is not trivial. We introduce an axiomatization of a class of processes we call scale-invariant random spatial networks, whose primitives are routes between each pair of points in the plane. One concrete model, based on minimum-time routes in a binary hierarchy of roads with different speed limits, has been shown to satisfy the axioms, and two other constructions (based on Poisson line processes and on dynamic proximity graphs) are expected also to do so. We initiate study of structure theory and summary statistics for general processes in the class. Many questions arise in this setting via analogies with diverse existing topics, from geodesics in first-passage percolation to transit node-based route-finding algorithms.

Five statistical questions about the tree of life.

Stochastic modeling of phylogenies raises five questions that have received varying levels of attention from quantitatively inclined biologists. 1) How large do we expect (from the model) the ratio of maximum historical diversity to current diversity to be? 2) From a correct phylogeny of the extant species of a clade, what can we deduce about past speciation and extinction rates? 3) What proportion of extant species are in fact descendants of still-extant ancestral species, and how does this compare with predictions of models? 4) When one moves from trees on species to trees on sets of species (whether traditional higher order taxa or clades within PhyloCode), does one expect trees to become more unbalanced as a purely logical consequence of tree structure, without signifying any real biological phenomenon? 5) How do we expect that fluctuation rates for counts of higher order taxa should compare with fluctuation rates for number of species? We present a mathematician's view based on an oversimplified modeling framework in which all these questions can be studied coherently.

Dimerization of ß-tryptase inhibitors, does it work for both basic and neutral P1 groups?

The tetrameric folding of ß-tryptase and the pair-wise distribution of its substrate binding sites offer a unique opportunity for development of inhibitors that span two adjacent binding sites. A series of dimeric inhibitors with two basic P1 moieties was discovered using this design strategy and exhibited tight-binder characteristics. Using the same strategy, an attempt was made to design and synthesize dimeric inhibitors with two neutral-P1 groups in hope to exploit the dimeric binding mode to achieve a starting point for further optimization. The unsuccessful attempt, however, demonstrated the important role played by Ala190 in neutral-P1 binding and casted further doubt on the possibility of developing neutral-P1 inhibitors for ß-tryptase.

A new chain structure: catena-poly[4,4'-(ethane-1,2-diyl)dipyridinium bis[[aquadifluoridooxidovanadate]-mu-fluorido]].

The title compound, {(C(12)H(12)N(2))[V(2)F(6)O(2)(H(2)O)(2)]}(n), features a novel extended-chain moiety, [VOF(2)F(2/2)(H(2)O)](n), comprising trans vertex-connected VOF(4)(H(2)O) octahedra. The octahedra themselves show the characteristic distortion due to the off-centering of the V(4+) ion, such that a short terminal V=O bond and an elongated trans V-OH(2) bond are present. Hydrogen bonding from the water molecules to terminal F atoms in adjacent chains generates associated chain dimers, which are loosely linked into sheets via additional hydrogen bonding involving the organic moieties. Structural relationships with previously described vanadium oxyfluoride species are briefly discussed.

"If the land is healthy ... it makes the people healthy": the relationship between caring for Country and health for the Yorta Yorta Nation, Boonwurrung and Bangerang Tribes.

This article reports on research undertaken with members of three Indigenous groups in Victoria, Australia, to explore the health and wellbeing implications of caring for Country (defined as having knowledge, sense of responsibility and inherent right to be involved in the management of traditional lands). The research findings provide a better understanding of this key determinant of the health and wellbeing of Indigenous people in the context of public health where there are few existing published studies assessing this relationship. Thirteen traditional custodians(1) and local Indigenous environmental workers were interviewed. This qualitative study involving semi-structured interviews identified that caring for Country offers great benefits, including building self-esteem, fostering self-identity, maintaining cultural connection and enabling relaxation and enjoyment through contact with the natural environment. Results generated indicate that caring for Country may offer a means of improving the current poor health status of Indigenous Australian peoples.

Optimal geometry of transportation networks.

Motivated by the shape of transportation networks such as subways, we consider a distribution of points in the plane and ask for the network G of given length L that is optimal in a certain sense. In the general model, the optimality criterion is to minimize the average (over pairs of points chosen independently from the distribution) time to travel between the points, where a travel path consists of any line segments in the plane traversed at slow speed and any route within the subway network traversed at a faster speed. Of major interest is how the shape of the optimal network changes as L increases. We first study the simplest variant of this problem where the optimization criterion is to minimize the average distance from a point to the network, and we provide some general arguments about the optimal networks. As a second variant we consider the optimal network that minimizes the average travel time to a central destination, and we discuss both analytically and numerically some simple shapes such as the star network, the ring, or combinations of both these elements. Finally, we discuss numerically the general model where the network minimizes the average time between all pairs of points. For this case, we propose a scaling form for the average time that we verify numerically. We also show that in the medium-length regime, as L increases, resources go preferentially to radial branches and that there is a sharp transition at a value L_{c} where a loop appears.

A short synthesis of (+/-)-epiasarinin.

[reaction: see text] Epiasarinin, an endo-endo furofuran, has been synthesized from piperonal via a five-step route with good stereocontrol. The sequence involves Darzens condensation, alkenyl epoxide-dihydrofuran rearrangement, and a Lewis acid mediated cyclization.

Metal-organic frameworks for the storage and delivery of biologically active hydrogen sulfide.

Hydrogen sulfide is an extremely toxic gas that is also of great interest for biological applications when delivered in the correct amount and at the desired rate. Here we show that the highly porous metal-organic frameworks with the CPO-27 structure can bind the hydrogen sulfide relatively strongly, allowing the storage of the gas for at least several months. Delivered gas is biologically active in preliminary vasodilation studies of porcine arteries, and the structure of the hydrogen sulfide molecules inside the framework has been elucidated using a combination of powder X-ray diffraction and pair distribution function analysis.

An ionothermally prepared S = 1/2 vanadium oxyfluoride kagome lattice.

Frustrated magnetic lattices offer the possibility of many exotic ground states that are of great fundamental importance. Of particular significance is the hunt for frustrated spin-1/2 networks as candidates for quantum spin liquids, which would have exciting and unusual magnetic properties at low temperatures. The few reported candidate materials have all been based on d(9) ions. Here, we report the ionothermal synthesis of [NH(4)](2)[C(7)H(14)N][V(7)O(6)F(18)], an inorganic-organic hybrid solid that contains a S = 1/2 kagome network of d(1) V(4+) ions. The compound exhibits a high degree of magnetic frustration, with significant antiferromagnetic interactions but no long-range magnetic order or spin-freezing above 2 K, and appears to be an excellent candidate for realizing a quantum spin liquid ground state in a spin-1/2 kagome network.

Protecting group and switchable pore-discriminating adsorption properties of a hydrophilic-hydrophobic metal-organic framework.

Formed by linking metals or metal clusters through organic linkers, metal-organic frameworks are a class of solids with structural and chemical properties that mark them out as candidates for many emerging gas storage, separation, catalysis and biomedical applications. Important features of these materials include their high porosity and their flexibility in response to chemical or physical stimuli. Here, a copper-based metal-organic framework has been prepared in which the starting linker (benzene-1,3,5-tricarboxylic acid) undergoes selective monoesterification during synthesis to produce a solid with two different channel systems, lined by hydrophilic and hydrophobic surfaces, respectively. The material reacts differently to gases or vapours of dissimilar chemistry, some stimulating subtle framework flexibility or showing kinetic adsorption effects. Adsorption can be switched between the two channels by judicious choice of the conditions. The monoesterified linker is recoverable in quantitative yield, demonstrating possible uses of metal-organic frameworks in molecular synthetic chemistry as 'protecting groups' to accomplish selective transformations that are difficult using standard chemistry techniques.

Stochastic models for phylogenetic trees on higher-order taxa.

Simple stochastic models for phylogenetic trees on species have been well studied. But much paleontology data concerns time series or trees on higher-order taxa, and any broad picture of relationships between extant groups requires use of higher-order taxa. A coherent model for trees on (say) genera should involve both a species-level model and a model for the classification scheme by which species are assigned to genera. We present a general framework for such models, and describe three alternate classification schemes. Combining with the species-level model of Aldous and Popovic (Adv Appl Probab 37:1094-1115, 2005), one gets models for higher-order trees, and we initiate analytic study of such models. In particular we derive formulas for the lifetime of genera, for the distribution of number of species per genus, and for the offspring structure of the tree on genera.

Hydrothermal chemistry of oligomeric vanadium oxyfluorides.

Nine new vanadium oxyfluorides, containing ten different oligomeric vanadium (oxy)fluoride anions have been prepared by solvothermal synthesis in water-ethylene glycol and using organic cations as co-crystallising agents. Crystal structures are reported for each. Amongst the ten structure types, five represent previously unobserved moieties, including one monomeric unit (cis-[VOF4(H2O)]2-), two dimers ([V2O2F6(H2O)2]2- and [V2O2F8]4-) and two tetramers (both isomers of composition [V4O4F14]6-). Structural relationships between the various units are discussed, together with some rationalisation of their occurrence as a function of synthetic variables.

Hydrothermal vanadium fluoride chemistry: four new V3+ chain structures.

An exploratory study of the hydrothermal chemistry of vanadium in HF solutions has resulted in the preparation of four new vanadium (III) fluorides with chainlike structural motifs. [NH4]2[VF5] (1) and [C2N2H10][VF5] (2) feature infinite chains of trans corner-sharing VF4F2/2 octahedra, [C4N2H6][VF5].H2O (3) has cis corner-sharing [VF4F2/2]infinity chains, and [C10N2H8][VF3] (4) has trans corner-sharing [VF2F2/2]infinity chains bridged into sheets by the 4,4'-bipy linker. All four compounds exhibit antiferromagnetic behavior.

Novel vanadium(IV) oxyfluorides with 'spin-ladder'-like structures, and their relationship to (VO)2P2O7.

Three novel vanadium(IV) oxyfluorides have been prepared by hydrothermal synthesis. All three materials feature 'ladder'-like chains of edge- and corner-sharing V(O/F) octahedra, topologically similar to those in (VO)2P2O7. CsVOF3 and RbVOF3 are isostructural, whereas in (bpeH2)1/2[VOF3] (bpe = trans-1,2-bis(4-pyridyl)-ethylene) inclusion of the organic structure-directing agent affects both the conformation of the ladders and their packing within the unit cell. Magnetic susceptibility data for each of the new materials have been fitted using a spin-1/2 Heisenberg antiferromagnetic chain model, which shows that the predominant magnetic interactions act along the 'legs' of the ladder, with negligible interactions both along the 'rungs' and between neighboring chains. This behavior contrasts markedly with that of (VO)2P2O7 itself.

The dihydrofuran template approach to furofuran synthesis.

Flash vacuum pyrrolysis of vinyl epoxides provides cis-dihydrofuran carboxylic esters in good yields and diastereoselectivities, which, on base-promoted epimerisation afford the complementary trans series. The compounds provide a viable template for a Lewis acid promoted cyclisation to provide the 2,6-diaryl-3,7-dioxabicyclo[3.3.0]octane core found in the furofuran series of natural lignans. This strategy is stereodivergent and can be controlled to provide the exo-exo, exo-endo or endo-endo stereochemistries. The approach has been exemplified in syntheses of the sesamyl furofurans (+/-)-epiasarinin and (+/-)-asarinin.

Role of cathepsin S-dependent epithelial cell apoptosis in IFN-gamma-induced alveolar remodeling and pulmonary emphysema.

Th1/Tc1 inflammation and remodeling responses characterized by tissue atrophy and destruction frequently coexist in human diseases and disorders. However, the mechanisms that are used by Th1/Tc1 cytokines, like IFN-gamma, to induce these responses have not been defined. To elucidate the mechanism(s) of IFN-gamma-induced tissue remodeling and destruction, we characterized the pathway that lung-targeted, transgenic IFN-gamma uses to induce alveolar remodeling in a murine pulmonary emphysema modeling system. In these mice, transgenic IFN-gamma caused epithelial cell DNA injury and apoptosis detectable with TUNEL (Roche) and dual annexin V and propidium iodide staining. These responses were associated with death receptor and mitochondrial apoptosis pathway activation. Importantly, apoptosis inhibition with a caspase inhibitor (N-benzylcarboxy-Val-Ala-Asp-fluoromethyl-ketone) or a null mutation of caspase-3 blocked this DNA injury and apoptosis response and significantly ameliorated IFN-gamma-induced emphysema. These interventions also ameliorated IFN-gamma-induced inflammation and decreased pulmonary protease burden. Selective cathepsin S inhibition and a null mutation of cathepsin S also decreased IFN-gamma-induced DNA injury, apoptosis, emphysema, inflammation, and protease accumulation. These studies demonstrate that cathepsin S-dependent epithelial cell apoptosis is a critical event in the pathogenesis of IFN-gamma-induced alveolar remodeling and emphysema. They also link inflammation, protease/antiprotease alterations, and protease-dependent apoptosis in the pathogenesis of Th1/Tc1 cytokine-induced tissue remodeling and destructive responses.

Scaling and universality in continuous length combinatorial optimization.

We consider combinatorial optimization problems defined over random ensembles and study how solution cost increases when the optimal solution undergoes a small perturbation delta. For the minimum spanning tree, the increase in cost scales as delta2. For the minimum matching and traveling salesman problems in dimension d >/= 2, the increase scales as delta3; this is observed in Monte Carlo simulations in d = 2, 3, 4 and in theoretical analysis of a mean-field model. We speculate that the scaling exponent could serve to classify combinatorial optimization problems of this general kind into a small number of distinct categories, similar to universality classes in statistical physics.

A general strategy for the diastereoselective synthesis of 2,6-diaryl-3,7-dioxabicyclo[3.3.0]octane lignans.

A strategy for the stereoselective synthesis of all the possible diastereoisomers of the 2,6-diaryl-3,7-dioxabicyclo[3.3.0]octane (furofuran) lignans from a single dihydrofuran precursor is described. The key steps involve a diastereocontrolled templated cationic cyclization followed by stereoselective reduction of the resulting methyl glycoside.

Phosphorus-nitrogen-phosphorus ligands: cooperative effects between nitrogen and phosphorus substituents on catalytic activity.

A new generation of PNP compounds bearing different diarylphosphine groups were prepared and used as ligands in palladium-catalysed Suzuki cross-coupling reactions. Rates of oxidative addition of iodobenzene to (PNP)Pd[0] complexes were measured using UV spectroscopy. Synergistic effects between the N- and P- substituents were identified and correlated in redox and catalytic chemistry.

Potent small molecule inhibitors of spleen tyrosine kinase (Syk).

A series of oxindoles demonstrating inhibition of the phosphorylation of biotinylated substrates of Syk and IgE/Fc epsilon RI triggered basophil cell degranulation has been identified. A study of the SAR around sulfonamide 31 (IC(50)=5 nM, EC(50)=1400 nM) is discussed. The modest cellular activity representative of the sulfonamide series was overcome when the Polar Surface Area was lowered to <110 A(2), leading to the identification of amide 32 (IC(50)=145 nM, EC(50)=100 nM).