Design of experiment for the optimisation of deep reactive ion etching of silicon inserts for micro-fabrication

The following paper describes a design of experiments investigation of the deep reactive of pillar structures on a silicon wafer. The etched wafers would subsequently be used as masters for the fabrication of nickel mould inserts for microinjection moulding. Undercuts occur when the pillar base has a smaller cross-section than the apex of the pillar. They therefore affect tolerances of the subsequent nickel mould, its strength and its de-mouldability from the silicon form. The response measured in these experiments was the degree of undercut of micro-scale (10 μm x 10 μm x 40 μm, 5 μm x 5 μm x 40 μm and 2 μm x 2 μm x 40 μm) The literature suggests that gas pressure, platen power, gas flow rate, phase switching times and mask size can all affect the degree of undercut. After examination of this literature, and of manufacturers guidelines, three parameters were selected for experimental testing: platen power, C 4F 8 gas flow rate during the passivation phase and switching times. Switching times was found to be the only statistically significant parameter for both 10x10 μm and 5x5 μm pillars. The 2x2 μm pillars were not successfully replicated and could therefore not undergo statistical evaluation

Sphagnum physiology in the context of changing climate: emergent influences of genomics, modelling and host-microbiome interactions on understanding ecosystem function.

Peatlands harbour more than one-third of terrestrial carbon leading to the argument that the bryophytes, as major components of peatland ecosystems, store more organic carbon in soils than any other collective plant taxa. Plants of the genus Sphagnum are important components of peatland ecosystems and are potentially vulnerable to changing climatic conditions. However, the response of Sphagnum to rising temperatures, elevated CO2 and shifts in local hydrology have yet to be fully characterized. In this review, we examine Sphagnum biology and ecology and explore the role of this group of keystone species and its associated microbiome in carbon and nitrogen cycling using literature review and model simulations. Several issues are highlighted including the consequences of a variable environment on plant-microbiome interactions, uncertainty associated with CO2 diffusion resistances and the relationship between fixed N and that partitioned to the photosynthetic apparatus. We note that the Sphagnum fallax genome is currently being sequenced and outline potential applications of population-level genomics and corresponding plant photosynthesis and microbial metabolic modelling techniques. We highlight Sphagnum as a model organism to explore ecosystem response to a changing climate and to define the role that Sphagnum can play at the intersection of physiology, genetics and functional genomics

A Combined Therapeutic Regimen of Buspirone and Environmental Enrichment is more Efficacrious than Either Alone in Enhancing Spatial Learning in Brain-Injured Rats

Abstract Buspirone, a 5-HT1A receptor agonist, and environmental enrichment (EE) enhance cognition and reduce histopathology after traumatic brain injury (TBI) in adult rats, but have not been fully evaluated after pediatric TBI, which is the leading cause of death in children. Hence, the aims of this study were to assess the efficacy of buspirone alone (Experiment 1) and in combination with EE (Experiment 2) in TBI postnatal day-17 male rats. The hypothesis was that both therapies would confer cognitive and histological benefits when provided singly, but their combination would be more efficacious. Anesthetized rats received a cortical impact or sham injury and then were randomly assigned to receive intraperitoneal injections ofbuspirone (0.08 mg/kg, 0.1 mg/kg, and 0.3 mg/kg) or saline vehicle (1.0 mL/kg) 24 h after surgery and once daily for 16 days (Experiment 1). Spatial learning and memory were assessed using the Morris water maze (MWM) on post-operative days 11-16, and cortical lesion volume was quantified on day 17. Sham controls for each condition were significantly better than all TBI groups. In the TBI groups, buspirone (0.1 mg/kg) enhanced MWM performance versus vehicle and buspirone (0.08 mg/kg and 0.3 mg/kg) (p\u3c0.05) and reduced lesion volume relative to vehicle (p=0.038). In Experiment 2, buspirone (0.1 mg/kg) or vehicle was combined with EE after TBI, and the data were compared to the standard (STD)-housed groups from Experiment 1. EE lead to a significant enhancement of spatial learning and a reduction in lesion size versus STD. Moreover, the combined treatment group (buspirone+EE) performed markedly better than the buspirone+STD and vehicle+EE groups, which suggests an additive effect and supports the hypothesis. The data replicate previous studies assessing these therapies in adult rats. These novel findings may have important rehabilitation-relevant implications for clinical pediatric TBI

Distribution of lutzomyia longipalpis chemotype populations in Sao Paulo state, Brazil

American visceral leishmaniasis (AVL) is an emerging disease in the state of Sao Paulo, Brazil. Its geographical expansion and the increase in the number of human cases has been linked to dispersion of Lutzomyia longipalpis into urban areas. To produce more accurate risk maps we investigated the geographic distribution and routes of expansion of the disease as well as chemotype populations of the vector. A database, containing the annual records of municipalities which had notified human and canine AVL cases as well as the presence of the vector, was compiled. The chemotypes of L. longipalpis populations from municipalities in different regions of Sao Paulo State were determined by Coupled Gas Chromatography - Mass Spectrometry. From 1997 to June 2014, L. longipalpis has been reported in 166 municipalities, 148 of them in the Western region. A total of 106 municipalities were identified with transmission and 99 were located in the Western region, where all 2,204 autochthonous human cases occurred. Both the vector and the occurrence of human cases have expanded in a South-easterly direction, from the Western to central region, and from there, a further expansion to the North and the South. The (S)-9-methylgermacrene-B population of L. longipalpis is widely distributed in the Western region and the cembrene-1 population is restricted to the Eastern region. The maps in the present study show that there are two distinct epidemiological patterns of AVL in Sao Paulo State and that the expansion of human and canine AVL cases through the Western region has followed the same dispersion route of only one of the two species of the L. longipalpis complex, (S)-9-methylgermacrene-B. Entomological vigilance based on the routes of dispersion and identification of the chemotype population could be used to identify at-risk areas and consequently define the priorities for control measures93COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESSuperintendencia de Controle de Endemias (SUCEN); Wellcome Trus

Structural Basis of Chemokine Sequestration by a Tick Chemokine Binding Protein: The Crystal Structure of the Complex between Evasin-1 and CCL3

Chemokines are a subset of cytokines responsible for controlling the cellular migration of inflammatory cells through interaction with seven transmembrane G protein-coupled receptors. The blocking of a chemokine-receptor interaction results in a reduced inflammatory response, and represents a possible anti-inflammatory strategy, a strategy that is already employed by some virus and parasites. Anti-chemokine activity has been described in the extracts of tick salivary glands, and we have recently described the cloning and characterization of such chemokine binding proteins from the salivary glands, which we have named Evasins.We have solved the structure of Evasin-1, a very small and highly selective chemokine-binding protein, by x-ray crystallography and report that the structure is novel, with no obvious similarity to the previously described structures of viral chemokine binding proteins. Moreover it does not possess a known fold. We have also solved the structure of the complex of Evasin-1 and its high affinity ligand, CCL3. The complex is a 1:1 heterodimer in which the N-terminal region of CCL3 forms numerous contacts with Evasin-1, including prominent pi-pi interactions between residues Trp89 and Phe14 of the binding protein and Phe29 and Phe13 of the chemokine.However, these interactions do not appear to be crucial for the selectivity of the binding protein, since these residues are found in CCL5, which is not a ligand for Evasin-1. The selectivity of the interaction would appear to lie in the N-terminal residues of the chemokine, which form the "address" whereas the hydrophobic interactions in the rest of the complex would serve primarily to stabilize the complex. A thorough understanding of the binding mode of this small protein, and its other family members, could be very informative in the design of potent neutralizing molecules of pro-inflammatory mediators of the immune system, such as chemokines

The p110 delta structure: mechanisms for selectivity and potency of new PI(3)K inhibitors.

Deregulation of the phosphoinositide-3-OH kinase (PI(3)K) pathway has been implicated in numerous pathologies including cancer, diabetes, thrombosis, rheumatoid arthritis and asthma. Recently, small-molecule and ATP-competitive PI(3)K inhibitors with a wide range of selectivities have entered clinical development. In order to understand the mechanisms underlying the isoform selectivity of these inhibitors, we developed a new expression strategy that enabled us to determine to our knowledge the first crystal structure of the catalytic subunit of the class IA PI(3)K p110 delta. Structures of this enzyme in complex with a broad panel of isoform- and pan-selective class I PI(3)K inhibitors reveal that selectivity toward p110 delta can be achieved by exploiting its conformational flexibility and the sequence diversity of active site residues that do not contact ATP. We have used these observations to rationalize and synthesize highly selective inhibitors for p110 delta with greatly improved potencies

A gas-rich nuclear bar fuelling a powerful central starburst in NGC 2782

We present evidence that the peculiar interacting starburst galaxy NGC 2782 (Arp 215) harbors a gas-rich nuclear stellar bar feeding an M82-class powerful central starburst, from a study based on OVRO CO (J=1->0) data, WIYN BVR & Halpha observations, along with available NIR images, a 5 GHz RC map and HST images. NGC 2782 harbors a clumpy, bar-like CO feature of radius ~ 7.5'' (1.3 kpc) which leads a nuclear stellar bar of similar size. The nuclear CO bar is massive: it contains ~2.5x10**9 M_sun of molecular gas, which makes up ~ 8 % of the dynamical'mass present within a 1.3 kpc radius. Within the CO bar, emission peaks in two extended clumpy lobes which lie on opposite sides of the nucleus, separated by ~ 6'' (1 kpc). Between the CO lobes, in the inner 200 pc radius, resides a powerful central starburst which is forming stars at a rate of 3 to 6 M_sun yr-1. While circular motions dominate the CO velocity field, the CO lobes show weak bar-like streaming motions on the leading side of the nuclear stellar bar, suggestive of gas inflow. We estimate semi-analytically the gravitational torque from the nuclear stellar bar on the gas, and suggest large gas inflow rates from the CO lobes into the central starburst. These observations, which are amongst the first ones showing a nuclear stellar bar fuelling molecular gas into an intense central starburst, are consistent with simulations and theory which suggest that nuclear bars provide an efficient way of transporting gas closer to the galactic center to fuel central activity. Furthermore, several massive clumps are present at low radii, and dynamical friction might produce further gas inflow. We suggest that the nuclear molecular gas bas and central activity will be very short-lived, likely disappearing within 5x10**8 years.Comment: Accepted by the Astrophysical Journal, 10 pages, Latex with emulateapj.sty, apjfonts.sty, 10 postscript & 2 gif figure

KLF9 and JNK3 Interact to Suppress Axon Regeneration in the Adult CNS

Neurons in the adult mammalian CNS decrease in intrinsic axon growth capacity during development in concert with changes in Krüppel-like transcription factors (KLFs). KLFs regulate axon growth in CNS neurons including retinal ganglion cells (RGCs). Here, we found that knock-down of KLF9, an axon growth suppressor that is normally upregulated 250-fold in RGC development, promotes long-distance optic nerve regeneration in adult rats of both sexes. We identified a novel binding partner, MAPK10/JNK3 kinase, and found that JNK3 (c-Jun N-terminal kinase 3) is critical for KLF9\u27s axon-growth-suppressive activity. Interfering with a JNK3-binding domain or mutating two newly discovered serine phosphorylation acceptor sites, Ser106 and Ser110, effectively abolished KLF9\u27s neurite growth suppression in vitro and promoted axon regeneration in vivo. These findings demonstrate a novel, physiologic role for the interaction of KLF9 and JNK3 in regenerative failure in the optic nerve and suggest new therapeutic strategies to promote axon regeneration in the adult CNS

Microspatial Distributional Patterns of Vectors of Cutaneous Leishmaniasis in Pernambuco, Northeastern Brazil

This is the publisher's version, also available electronically from http://www.hindawi.com/journals/jtm/2012/642910/abs/The purpose of this study is to analyze the spatial distribution and population trends through time of Lutzomyia species in a long-term focus of cutaneous leishmaniasis transmission in an Atlantic Forest area, northeastern Brazil. Sand fly populations of different ecological niches were monitored spatiotemporally in 2009. To summarize vegetation characteristics and phenology, we calculated the Normalized Difference Vegetation Index from Landsat images. Using niche modeling approaches, we assessed suites of environmental factors to identify areas of transmission risk. Although 12 species were detected, L. whitmani was the most abundant and broadly distributed across the area, particularly in peridomiciliary locations, and associated negatively with denser vegetation areas. On the other hand, L. complexa, L. sordelli, and L. tupynambai were found almost exclusively in forested areas ( < 0 . 0 5 ), and associated positively with denser vegetation. Lutzomyia species' occurrences are related to specific environmental combinations (with contrast among species) in the region