New insight into the architecture of oxy-anion pocket in unliganded conformation of GAT domains: A MD-simulation study

Human Guanine Monophosphate Synthetase (hGMPS) converts XMP to GMP, and acts as a bifunctional enzyme with N-terminal ``glutaminase'' (GAT) and C-terminal ``synthetase'' domain. The enzyme is identified as a potential target for anticancer and immunosuppressive therapies. GAT domain of enzyme plays central role in metabolism, and contains conserved catalytic residues Cys104, His190, and Glu192. MD simulation studies on GAT domain suggest that position of oxyanion in unliganded conformation is occupied by one conserved water molecule (W1), which also stabilizes that pocket. This position is occupied by a negatively charged atom of the substrate or ligand in ligand bound crystal structures. In fact, MD simulation study of Ser75 to Val indicates that W1 conserved water molecule is stabilized by Ser75, while Thr152, and His190 also act as anchor residues to maintain appropriate architecture of oxyanion pocket through water mediated H-bond interactions. Possibly, four conserved water molecules stabilize oxyanion hole in unliganded state, but they vacate these positions when the enzyme (hGMPS)-substrate complex is formed. Thus this study not only reveals functionally important role of conserved water molecules in GAT domain, but also highlights essential role of other non-catalytic residues such as Ser75 and Thr152 in this enzymatic domain. The results from this computational study could be of interest to experimental community and provide a testable hypothesis for experimental validation. Conserved sites of water molecules near and at oxyanion hole highlight structural importance of water molecules and suggest a rethink of the conventional definition of chemical geometry of inhibitor binding site.

Density control of ZnO nanowires grown using Au-PMMA nanoparticles and their growth behavior.

Au nanoparticles stabilized by poly(methyl methacrylate) (PMMA) were used as a catalyst to grow vertically aligned ZnO nanowires (NWs). The density of ZnO NWs with very uniform diameter was controlled by changing the concentration of Au-PMMA nanoparticles (NPs). The density was in direct proportion to the concentration of Au-PMMA NPs. Furthermore, the growth process of ZnO NWs using Au-PMMA NPs was systematically investigated through comparison with that using Au thin film as a catalyst. Au-PMMA NPs induced polyhedral-shaped bases of ZnO NWs separated from each other, while Au thin film formed a continuous network of bases of ZnO NWs. This approach provides a facile and cost-effective catalyst density control method, allowing us to grow high-quality vertically aligned ZnO NWs suitable for many viable applications.

Formation of metastable liquid catalyst during subeutectic growth of germanium nanowires.

Lattice-resolved, video-rate environmental transmission electron microscopy shows the formation of a liquid Au-Ge layer on sub-30-nm Au catalyst crystals and the transition of this two-phase Au-Ge/Au coexistence to a completely liquid Au-Ge droplet during isothermal digermane exposure at temperatures far below the bulk Au-Ge eutectic temperature. Upon Ge crystal nucleation and subsequent Ge nanowire growth, the catalyst either recrystallizes or remains liquid, apparently stabilized by the Ge supersaturation. We argue that there is a large energy barrier to nucleate diamond-cubic Ge, but not to nucleate the Au-Ge liquid. As a result, the system follows the more kinetically accessible path, forming a liquid even at 240 degrees C, although there is no liquid along the most thermodynamically favorable path below 360 degrees C.

Influence of surfactant solubility on the deformation and breakup of a bubble or capillary jet in a viscous fluid

In a previous study [M. Hameed, J. Fluid Mech. 594, 307 (2008)] the authors investigated the influence of insoluble surfactant on the evolution of a stretched, inviscid bubble surrounded by a viscous fluid via direct numerical simulation of the Navier-Stokes equations, and showed that the presence of surfactant can cause the bubble to contract and form a quasisteady slender thread connecting parent bubbles, instead of proceeding directly toward pinch-off as occurs for a surfactant-free bubble. Insoluble surfactant significantly retards pinch-off and the thread is stabilized by a balance between internal pressure and reduced capillary pressure due to a high concentration of surfactant that develops during the initial stage of contraction. In the present study we investigate the influence of surfactant solubility on thread formation. The adsorption-desorption kinetics for solubility is in the diffusion controlled regime. A long-wave model for the evolution of a capillary jet is also studied in the Stokes flow limit, and shows dynamics that are similar to those of the evolving bubble. With soluble surfactant, depending on parameter values, a slender thread forms but can pinch-off later due to exchange of surfactant between the interface and exterior bulk flow. © 2009 American Institute of Physics.

Fabrication and properties of TBCCO films via air-atomising spray deposition of thallium-free precursors

The high-field properties of polycrystalline superconducting TlBaCaCuO films fabricated by the incorporation of thallium vapour into air-atomised BaCaCuO precursors are described. Thick films with Tc values in the range 106-111 K have been prepared on polycrystalline yttria-stabilised zirconia substrates. The surface morphology, crystal structure and composition of the films are related to their high-field transport and magnetisation properties. Typical 10 mm × 9 mm films show Jc values > 1×104 A/cm2 at 77 K (0 T). The best film has a Jc=1.3×104 A/cm2 (Ic=3.6 A) at 77 K (0 T). Films prepared on 26 mm×9 mm substrates show typical large-area Jc values > 0.5×104 A/cm2 (77 K, 0 T). A square planar specimen of dimensions 4.3 mm ×4.3 mm exhibited magnetisation Jc values=1.2×105 A/cm2 at 4.2 K (0.1 T), 9.3×104 A/cm2 at 10 K (0.1 T), 3.3×104 A/ cm2 at 4 K (8 T), and 1.6×104 A/cm2 at 10 K (8 T). © 1994.

Growth Mechanism And Corrosion Behavior Of Ceramic Coatings On Aluminum Produced By Autocontrol Ac Pulse Peo

Ceramic coatings are produced on aluminum alloy by autocontrol AC pulse Plasma Electrolytic Oxidation (PEO) with stabilized average current. Transient signal gathering system is used to study the current, voltage, and the transient wave during the PEO process. SEM, OM, XRD and EDS are used to study the coatings evolution of morphologies, composition and structure. TEM is used to study the micro profile of the outer looser layer and inner compact layer. Polarization test is used to study the corrosion property of PEO coatings in NaCl solution. According to the test results, AC pulse PEO process can be divided into four stages with different aspects of discharge phenomena, voltage and current. The growth mechanism of AC PEO coating is characterized as anodic reaction and discharge sintering effect. PEO coating can increase the corrosion resistance of aluminum alloy by one order or two; however, too long process time is not necessarily needed to increase the corrosion resistance. In condition of this paper, PEO coating at 60 min is the most protective coating for aluminum alloy substrate. (C) 2008 Elsevier B.V. All fights reserved.

Effect Of Load Triaxiality On Polymorphic Transitions In Zinc Oxide

Molecular dynamics (MD) simulations and first-principles calculations are carried out to analyze the stability of both newly discovered and previously known phases of ZnO under loading of various triaxialities. The analysis focuses on a graphite-like phase (FIX) and a body-centered-tetragonal phase (BCT-4) that were observed recently in [0 1 (1) over bar 0]- and [0 0 0 1]-oriented nanowires respectively under uniaxial tensile loading as well as the natural state of wurtzite (WZ) and the rocksalt (RS) phase which exists under hydrostatic pressure loading. Equilibrium critical stresses for the transformations are obtained. The WZ -> HX transformation is found to be energetically favorable above a critical tensile stress of 10 GPa in [0 1 (1) over tilde 0] nanowires. The BCT-4 phase can be stabilized at tensile stresses above 7 GPa in [0 0 0 1] nanowires. The RS phase is stable at hydrostatic pressures above 8.2 GPa. The identification and characterization of these phase transformations reveal a more extensive polymorphism of ZnO than previously known. A crystalline structure-load triaxiality map is developed to summarize the new understanding. (c) 2007 Elsevier Ltd. All rights reserved.

Asymptotic analysis of plane-strain mode I steady-state crack growth in transformation toughening ceramics (II)

Based on a constitutive law which includes the shear components of transformation plasticity, the asymptotic solutions to near-tip fields of plane-strain mode I steadity propagating cracks in transformed ceramics are obtained for the case of linear isotropic hardening. The stress singularity, the distributions of stresses and velocities at the crack tip are determined for various material parameters. The factors influencing the near-tip fields are discussed in detail.

O processo decisório legislativo na criação e reforma do Bacen e do CMN em 1964 e 1994 : incerteza, cooperação e resultados legislativos

Analisa o processo decisório legislativo nos casos da criação e reforma do Bacen e do CMN em 1964 e 1994, ocorridos no âmbito de planos exitosos de combate à inflação (PAEG e Plano Real, respectivamente). A definição de um formato institucional para a autoridade monetária é uma escolha dos legisladores em termos da produção da política pública de responsabilidade daqueles órgãos, que em ambos os casos foi importante na busca da estabilidade de preços. A partir da Teoria Política Formal utilizaram-se dados primários e fontes secundárias para construir modelo e hipóteses que consideraram as dimensões de interesse geral (combate à inflação) e de políticas particularistas/distributivistas (crédito rural e representação privada no CMN). Concluiu-se que em ambos os processos a iniciativa do Poder Executivo foi fundamental para o resultado final, contudo, em ambas as situações, mesmo durante o ano de 1964 (período militar), o Legislativo teve papel relevante na definição do formato final de ambas as decisões. No primeiro caso houve uma barganha entre os Poderes Executivo e Legislativo para aprovação da proposta, que envolveu concessões no sentido de garantir representação privada no CMN e a institucionalização do crédito rural. No segundo caso o uso da Medida Provisória caracterizou uma forma diferente de coordenação entre os poderes, em que a MP atuou para diminuir a incerteza em relação aos resultados do plano e às alterações na composição do CMN e assim permitir a aprovação da matéria. Os resultados da tese, favorecidos pela comparação de dois períodos diversos do sistema político brasileiro, colaboram com a análise das relações Executivo-Legislativo, sobretudo ao valorizar os instrumentos legislativos do Presidente da República e a forma de equacionamento da incerteza nos processos decisórios. Ainda, permite-se um maior conhecimento da realidade legislativa durante o ano de 1964, quando, ao menos para a Reforma Bancária, não se pode falar de solapamento dos poderes e prerrogativas do Congresso Nacional pelo governo militar.

Florida's West Coast inlets: shoreline effects and recommended action

This report responds to the 1986 Beaches Bill which, in recognition of the potential deleterious impact on Florida's beaches of inlets modified for navigation, mandated a study of those inlets with identification of recommended action to reduce the impacts. This report addresses west Coast inlets; East Coast inlets are the subject of a companion report. There are 37 inlets along that portion of Florida's West Coast commencing from Pensacola Bay Entrance to Caxambas Pass at the south end of Marco Island. Compared to those on the East Coast, most West Coast inlets have not had the deleterious effects on the adjacent beaches, yet all modified inlets without proper management have the potential of impacting unfavorably on the adjacent shorelines. Moreover, at present there is interest in opening three West Coast entrances which either have been open in the past (Midnight Pass) or which have opened occasionally (Navarre Pass and Entrance to Phillips Lake). A review of inlets in their natural condition demonstrates the presence of a shallow broad outer bar across which the longshore transport Occurs. These shallow and shifting bar features were unsuitable for navigation which in many cases has led to the deepening of the channels and fixing with one or two jetty structures. Inlets in this modified state along with inappropriate maintenance practices have the potential of placing great ero$ional stress along the adjacent beaches. Moreover. channel dredging can reduce wave sheltering of the shoreline by ebb tidal shoals and alter the equilibrium of the affected shoreline segments. The ultimate in poor sand management practice is the placement of good quality beach sand in water depths too great for the sand to reenter the longshore system under natural forces; depths of 12 ft. or less are considered appropriate for Florida in order to maintain the sand in the system. With the interference of the nearshore sediment transport processes by inlets modified for navigation, if the adjacent beaches are to be stabilized there must be an active monitoring program with commitment to placement of dredged material of beach quality on shoreline segments of documented need. Several East Coast inlets have such transfer facilities; however. the quantities of sand transferred should be increased. Although an evolution and improvement in the technical capability to manage sand resources in the vicinity of inlets is expected, an adequate capability exists today and a concerted program should be made to commence a scheduled implementation of this capability at those entrances causing greatest erosional stress on the adjacent shorelines. A brief summary review for each of the 37 West Coast inlets is presented including: a scaled aerial photograph, brief historical information, several items related to sediment losses at each inlet and special characteristics relevant to State responsibilities. For each inlet, where appropriate, the above infor~tion is utilized to develop a recommenced action. (PDF has 101 pages.)

New Oncogenic Drivers in Hepatocellular Carcinoma: Role of the RNA Binding Protein Hu antigen R

156 p. : graf.

Distribution of skipjack in the Pacific Ocean, based on records of incidental catches of the Japanese longline tuna fishery

ENGLISH: All available longline data on skipjack captured in the Pacific Ocean by Japanese research vessels (1949-1965) and from incidental skipjack catches by Japanese commercial vessels (1956-1964) were analyzed. As skipjack are not specifically sought by longline vessels, the data are limited. Considering this it was found that: longline gear captures skipjack of wider size-range and is more selective for larger skipjack than conventional fishing methods, i.e. pole-and-line and purse-seine; skipjack are widely and almost continuously distributed across the Pacific; throughout the year average hook-rates are greater in the southeastern Pacific than in the northwestern Pacific; areas of high hook-rate shift south during the second and third quarters and north during the first and fourth quarters; in the western Pacific the north-south range of the catch distribution was greatest in the first and fourth quarters; skipjack hook-rates are relatively high in the northwestern Pacific east of Japan only during the first and fourth quarters; the highest hook-rates were recorded in extensive areas along the equator (from lO°N to 20°8 between approximately 155°W-100°W); generally more skipjack were captured by research longline gear in water temperature ranges approaching both the upper and lower temperature limits of skipjack distribution (18-21C and 26-28C), than is the case in surface skipjack fisheries; tentative comparisons of longline skipjack catch distributions with Pacific current systems, suggests low skipjack abundance in both North Pacific Central and North Pacific Equatorial water; the sex ratio was 95 males : 63 females in a small sample of skipjack examined; longlines capture skipjack of three, and possibly more, age groups; in skipjack size-composition samples studied, the smaller modal group (65 cm) observed in January-March in the northwestern Pacific (1600E-180oE and 20oN-45°N) corresponds in size to the larger modal group appearing in the late-summer surface fishery off the Izu-Bonin Islands southeast of Japan, and also compares in modal size to the skipjack taken in the Hawaiian fishery in spring time; the analysis of skipjack catches by hook position on the longline and by death-rate studies, indicates that part of the catch is made while the gear is in motion near the surface, and a lesser part of the catch is made when the gear is stabilized at a depth of 70 to 140 m. A brief discussion is given, in the light of new information presented, on several hypotheses by other authors concerning the population structure and migration of skipjack in the Pacific Ocean. SPANISH: Se analizaron todos los datos disponibles de la pesca con palangre de barriletes capturados en el Océano Pacífico por barcos japoneses de investigación (1949-1965) y por las capturas incidentales de los barcos comerciales japoneses (1956-1964). Como los barcos palangreros específicamente, no persiguen al barrilete, los datos son limitados. Considerando ésto, se encontró: que el arte palangrero obtiene barriletes con una distribución más amplia de tallas, y es más selectivo en cuanto a los barriletes de mayor talla, que los métodos convencionales de pesca, Le. cañas de pescar y redes de cerco; el barrilete se encuentra amplia y casi continuamente distribuido a través del Pacífico; en todo el año, las tasas promedio de captura por anzuelo son superiores en el Pacífico sudoriental que las del Pacífico noroeste; las áreas con una tasa alta de captura por anzuelo, se cambian hacia el sur durante los trimestres segundo y tercero, y durante los trimestres primero y cuarto hacia el norte; en el Pacífico occidental la amplitud de la distribución de captura norte-sur, fue superior en los trimestres primero y cuarto; las tasas de captura por anzuelo de barrilete, son relativamente altas en el Pacífico noroeste al este del Japón, únicamente durante los trimestres primero y cuarto; las tasas de captura por anzuelo más altas fueron registradas en extensas áreas a lo largo del ecuador (desde los 10°N hasta los 20°S, aproximadamente entre los 155°W-100°W) ; generalmente las artes palangreras de investigación capturaron más barrilete en aguas en las que la temperatura se aproximaba a los límites más altos o bajos de la temperatura en la distribución del barrilete (18-21 C y 26-28 C), que en el caso de la pesca superficial de barrilete; las comparaciones tentativas de la captura de barrilete con palangre, con el sistema de las corrientes del Pacífico, sugieren una abundancia inferior de barrilete tanto en las aguas del Pacífico central del norte como en las del Pacífico ecuatorial del norte; la proporcíon sexual examinada en una pequeña muestra de barriletes, fue de 95 machos y 63 hembras; los palangreros capturan barriletes de tres grupos de edad y posiblemente de más; en las muestras estudiadas de la composición de las tallas de barrilete, el grupo modal más pequeño (65 cm), observado en enero-marzo en el Pacífico noroeste (160 0E-180° y 20 oN-45°N), corresponde en talla al grupo modal más grande que aparece en la pesca de superficie a fines del verano frente a las Islas Izu-Bonín al sudeste del Japón, y se compara también con la talla modal del barrilete obtenido en la pesca hawaiana en la época de primavera; el análisis de las capturas de barrilete por medio del estudio de la posición de los anzuelos en el palangre y por la tasa de mortalidad, indica que parte de la captura se efectúa cuando el equipo está en movimiento cerca a la superficie y una parte inferior de la captura se realiza, cuando las artes se estabilizan a una profundidad de 70 a 140 m. Se ofrece una breve discusión sobre varias hipótesis de otros autores, en vista de la nueva información presentada referente a la estructura poblacional y a la migración del barrilete en el Océano Pacífico. (PDF contains 100 pages.)

Der Krill im Südatlantik. Entwicklung der Bestände, der Fischerei und des Bestandsmanagements

Since 1976 the Institute of Sea Fisheries of the Federal Research Center for Fisheries, Hamburg, has been conducting long-term monitoring research on Antarctic krill in order to manage the stocks according to the precautionary approach. The krill stocks of the South Atlantic fluctuate seasonally as well as inter-annually in biomass and recruitment success. Following high densities in the late 1970s, the stocks are recently declining. Shortly after the onset of a commercial fishery the catches reached a maximum of around 500 000 t annually, but stabilized around 100 000 t during recent years. Actual survey results indicate mean krill densities in the South Atlantic of 21.4 g/m2, corresponding to 44 Mio. t. The potential yield and maximum catch rate was set at 4.0 Mio. t per year subdivided for the various CCAMLR Subareas. CCAMLR is expected to introduce further conservation measures to control the fishery in the convention area in the near future, however, there is still room for developing a krill fishery in the Antarctic.

Structure-function studies of serine hydrolases: synthesis of a gene for ∝-lytic protease and the purification and characterization of a mutant β-lactamase

The author has constructed a synthetic gene for ∝-lytic protease. Since the DNA sequence of the protein is not known, the gene was designed by using the reverse translation of ∝-lytic protease's amino acid sequence. Unique restriction sites are carefully sought in the degenerate DNA sequence to aid in future mutagenesis studies. The unique restriction sites are designed approximately 50 base pairs apart and their appropriate codons used in the DNA sequence. The codons used to construct the DNA sequence of ∝-lytic protease are preferred codons in E-coli or used in the production of β-lactamase. Codon usage is also distributed evenly to ensure that one particular codon is not heavily used. The gene is essentially constructed from the outside in. The gene is built in a stepwise fashion using plasmids as the vehicles for the ∝-lytic oligomers. The use of plasmids allows the replication and isolation of large quantities of the intermediates during gene synthesis. The ∝-lytic DNA is a double-stranded oligomer that has sufficient overhang and sticky ends to anneal correctly in the vector. After six steps of incorporating ∝-lytic DNA, the gene is completed and sequenced to ensure that the correct DNA sequence is present and that no mutations occurred in the structural gene.

β-lactamase is the other serine hydrolase studied in this thesis. The author used the class A RTEM-1 β- lactamase encoded on the plasmid pBR322 to investigate the roll of the conserved threonine residue at position 71. Cassette mutagenesis was previously used to generate all possible amino acid substitutions at position 71. The work presented here describes the purification and kinetic characterization of a T71H mutant previously constructed by S. Schultz. The mutated gene was transferred into plasmid pJN for expression and induced with IPTG. The enzyme is purified by column chromatography and FPLC to homogeneity. Kinetic studies reveal that the mutant has lower k_(cat) values on benzylpenicillin, cephalothin and 6-aminopenicillanic acid but no changes in k_m except for cephalothin which is approximately 4 times higher. The mutant did not change siginificantly in its pH profile compared to the wild-type enzyme. Also, the mutant is more sensitive to thermal denaturation as compared to the wild-type enzyme. However, experimental evidence indicates that the probable generation of a positive charge at position 71 thermally stabilized the mutant.

An evaluation of the pelagic primary productivity and potential fish yield of Kainji Lake, Nigeria

The environmental conditions of Kainji Lake from 1971/72 to date appear to have stabilized to a large extent, judging from the similarity of physico-chemical parameters investigated in this study over the period. Solar radiation (as reflected in variation in temperature) and pH have remained largely constant over the years, while conductivity (index of nutrient enrichment), though significantly higher in 1995/96, could be described as sporadic and needs further monitoring to ascertain its trend in the lake. While water transparency and dissolved oxygen were higher in 1971/72 compared to the other years, these increases cannot be said to be overwhelming. The lower transparency in 1995/96 was due to the exceptional flood of that year and may have also accounted for the poorer dissolved oxygen concentration compared to the other years due to its impact on photosynthesis. There is no evidence from this study to indicate that primary productivity has increased over the years. Consequently, the observed increase in fish yield by the KLFPP from CAS, which is corroborated by estimates from the MEI, cannot be supported on the basis of improved photosynthetic production. The phenomenal high levels of conductivity recorded during certain periods in 1995 (600 mu mhos cm super(-1)) are hitherto unknown in the lake and may indicate a trend towards nutrient enrichment. However, it is premature at this stage to conclude on its long-term impact on primary production and consequently, on fish yield. Secondly, the notion of overfishing in the 80s (Ita, 1993), may need to be further examined as low or dwindling catches could be due to a number of factors among which are the level of fishing effort, the type and efficiency of gears and the intensity of sampling. It would appear that with the intervention of KLFPP, the better management of the lake's fisheries would increase the current level of catch. It also needs to be examined how much of the clupeid fisheries, which is now known to account for a substantial proportion of the total fish yield in Kainji Lake, was included in the sampling of the 80s. (PDF contains 43 pages)