Increased potency of a novel complement factor 5a receptor antagonist in a rat model of inflammatory bowel disease

We have previously shown that complement factor 5a(C5a) plays a role in the pathogenesis of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats by using the selective, orally active C5a antagonist AcF-[OP(D-Cha) WR]. This study tested the efficacy and potency of a new C5a antagonist, hydrocinnamate (HC)-[OP(D-Cha) WR], which has limited intestinal lumenal metabolism, in this model of colitis. Analogs of AcF-[OP(D-Cha) WR] were examined for their susceptibility to alimentary metabolism in the rat using intestinal mucosal washings. One metabolically stable analog, HC-[OP(D-Cha)WR], was then evaluated pharmacokinetically and investigated at a range of doses (0.03 - 10 mg/kg/ day p.o.) in the 8-day rat TNBS- colitis model, against the comparator drug AcF-[OP(D-Cha) WR]. Using various amino acid substitutions, it was determined that the AcF moiety of AcF-[OP(D-Cha) WR] was responsible for the metabolic instability of the compound in intestinal mucosal washings. The analog HC-[OP( D-Cha) WR], equiactive in vitro to AcF-[OP(D-Cha) WR], was resistant to intestinal metabolism, but it displayed similar oral bioavailability to AcF-[OP(D-Cha) WR]. However, in the rat TNBS- colitis model, HC-[OP(D-Cha) WR] was effective at reducing mortality, colon edema, colon macroscopic scores, and increasing food consumption and body weights, at 10- to 30- fold lower oral doses than AcF-[OP( D-Cha) WR]. These studies suggest that resistance to intestinal metabolism by HC-[OP(D-Cha) WR] may result in increased local concentrations of the drug in the colon, thus affording efficacy with markedly lower oral doses than AcF-[OP(D-Cha) WR] against TNBS-colitis. This large increase in potency and high efficacy of this compound makes it a potential candidate for clinical development against intestinal diseases such as inflammatory bowel disease.

(Table 1) K-Ar age determinations on biotite from coarse sand within DSDP Sample 72-516F-76-4,107-115

Qualitative petrographic study of selected clastic horizons within the Eocene section of Hole 516F has revealed the presence of abundant fine-grained lithic fragments, probably volcanic, along with coarser fragments of quartz and feldspar apparently derived from a nearby plutonic terrain. In detail, poor sorting, presence of graded bedding, and an abundance of clay suggest these are turbidite horizons locally derived from a mixed volcanic/plutonic terrain, possibly with some direct contribution from contemporary volcanic ash falls. A progressive increase in plutonic versus volcanic components with time is, however, more consistent with an erosional origin for most of this material. Unusual euhedral dark biotite is abundant in several of the lower clastic horizons; it is most easily interpreted as microphenocrysts weathered in situ out of alkalic volcanic ash. Biotite separated from Sample 516F-76-4,107-115 cm, has been dated by the K-Ar method at about 46 Ma. Alkaline volcanoes active on the Rio Grande Rise in the middle Eocene would be the most probable source of this ash and would be consistent with other evidence for potassic, alkaline volcanism along the Rio Grande Rise and at the Tristan da Cunha hot spot.

Hemolymph ionic regulation and adjustments in gill (Na(+), K(+))-ATPase activity during salinity acclimation in the swimming crab Callinectes ornatus (Decapoda, Brachyura)

We evaluate hemolymph osmotic and ionic regulatory abilities and characterize a posterior gill microsomal (Na(+), K(+))-ATPase from the marine swimming crab, Callinectes ornatus, acclimated to 21 parts per thousand or 33 parts per thousand salinity. C ornatus is isosmotic after acclimation to 21 parts per thousand but is hyposmotic at 33 parts per thousand salinity; hemolymph ions do not recover initial levels on acclimation to 21 parts per thousand salinity but are anisoionic compared to ambient concentrations, revealing modest regulatory ability. NH(4)(+) modulates enzyme affinity for K(+), which increases 187-fold in crabs acclimated to 33%. salinity. The (Na(+), K(+))-ATPase redistributes into membrane fractions of different densities, suggesting that altered membrane composition results from salinity acclimation. ATP was hydrolyzed at maximum rates of 182.6 +/- 7.1 nmol Pi min(-1) mg(-1) (21 parts per thousand) and 76.2 +/- 3.5 nmol Pi min(-1) mg(-1) (33 parts per thousand), with little change in K(M) values (approximate to 50 mu mol L(-1)). K(+) together with NH(4)(+) synergistically stimulated activity to maximum rates of approximate to 240 nmol Pi min(-1) mg(-1). K, values for ouabain inhibition (approximate to 110 mu mol L(-1)) decreased to 44.9 +/- 1.0 mu mol L(-1) (21 parts per thousand) and 28.8 +/- 1.3 mu mol L(-1) (33 parts per thousand) in the presence of both K(+) and NH(4)(+). Assays employing various inhibitors suggest the presence of mitochondrial F(0)F(1)- and K(+)- and V-ATPase activities in the gill microsomes. (C) 2009 Elsevier Inc. All rights reserved.

Açaí (Euterpe oleracea mart.) e camu-camu (Myrciaria dubia (H.B.K.) Mc Vaugh) possuem ação anti anêmica?

Avaliou-se o impacto da utilização do açaí e camu-camu em pré-escolares de uma Unidade Filantrópica de Manaus-AM. Foram selecionadas 85 crianças voluntárias, de dois a seis anos incompletos, de ambos os sexos, distribuídas aleatoriamente em 5 grupos, tendo como fonte de ferro e vitamina C: açaí e açaí + camu-camu, perfazendo um total de 2 mg de ferro e 40 mg de ácido ascórbico, assim como o ferro aminoácido quelato na concentração de 1 e 2 mg de ferro. O ferro foi distribuído diariamente na colação por um período de 120 dias. Na caracterização da anemia considerou-se o ponto de corte de hemoglobina <11g/dL. Os resultados demonstraram que de um universo de 85 crianças 6 (7%) apresentaram um quadro de desnutrição crônica, sendo ao final da intervenção reduzido para 4 (4,7%). O maior impacto da utilização do açaí foi como fonte energética, refletido no ganho de peso significativo das crianças (1,76 kg), mesmo quando adicionado de camu-camu (1,69 kg). Em relação a concentração de hemoglobina, não foi constatada diferença significativa entre as crianças dos diferentes grupos, independente da fonte de ferro: açaí (0,71 g/dL); açaí + camu-camu (0,60 g/dL), Ferro 2 mg (0,88 g/dL); água (0,85 g/ dL) e Ferro 1 mg (0,54 g/dL). Entretanto, a recuperação de crianças anêmicas foi maior no grupo que recebeu ferro aminoácido quelato na concentração de 2 mg de ferro. Conclui-se que o açaí tem um grande potencial como fonte energética e pouca expressividade como fonte de ferro, mesmo adicionado de camu-camu.

Deficiência de macro e micronutrientes em cana-de-açúcar (Saccharum officinarum spp) variedade CB 41-76 cultivada em solução nutritiva

Mudas de cana-de-açúcar (Saccharum officinarum spp) cultivar CB 41-76 foram cultivadas em soluções nutritivas, omitindo - se por vez o N, P, K, Ca, Mg, S, B, Cu, Fe, Mn, Mo e Zn, com os seguintes objetivos: 1. Obter um quadro sintomatológico da morfologia externa e morfologia interna em função das carências; 2. Verificar o efeito da presença e omissão dos macronutrientes na composição química das folhas (+1, +2, +3); (+4, +5, +6); (+7, +8, +9) e nas bainhas (+4, +5, +6). Foram constatados e descritos os sintomas de carência dos macro e micronutrientes. As partículas subcelulares mais afetadas pelas carências foram os cloroplastos das células da bainha envolvente dos feixes libero lenhosos e do parênquima paliçadico adjacente ao limbo. Níveis nas folhas de plantas sadias e deficientes, expressos em porcentagem na materia seca, foram.

Acúmulo de N, K, Ca, Mg e S na matéria seca da parte aérea de mudas de cajueiro-anão-precoce submetidas a níveis crescentes de matéria orgânica

Com o objetivo de verificar os efeitos de níveis crescentes de matéria orgânica no acúmulo de macronutrientes de porta-enxertos de cajueiro-anão-precoce em 4 estádios de crescimento, foi conduzido experimento na área experimental do Departamento de Irrigação e Drenagem da Universidade Federal do Ceará, em Fortaleza, Ceará, no período de abril a junho de 1995. Utilizou-se como substrato mistura de solo e húmus de minhoca em proporções variadas. Para o plantio, utilizou-se semente de cajueiro-anão-precoce progênie CCP-76. Os tratamentos resultaram da aplicação de cinco níveis de matéria orgânica (0; 100; 200; 300 e 400 cm³/2,5kg solo) e 4 épocas de avaliação (15; 30; 45 e 60 dias após a germinação). O delineamento experimental foi o inteiramente casualizado, em esquema de parcela subdividida, com quatro repetições e seis plantas por parcela. Amostras do material vegetal foram submetidas à digestão nítricoperclórica, para determinação de K, Ca, Mg e S, respectivamente, e sulfúrica, para determinar o N. A adição de níveis crescentes de matéria orgânica ao substrato apresentou efeito linear positivo, para o N e K, atingindo o máximo para a dose de 400 cm3. Em relação aos efeitos das épocas, verificou-se efeito linear negativo. Quanto ao Ca, Mg e S, por serem considerados de baixa mobilidade no floema, estes apresentaram tendências de concentração com o incremento de massa seca das mudas.

Epidemic K-Means clustering

The K-Means algorithm for cluster analysis is one of the most influential and popular data mining methods. Its straightforward parallel formulation is well suited for distributed memory systems with reliable interconnection networks. However, in large-scale geographically distributed systems the straightforward parallel algorithm can be rendered useless by a single communication failure or high latency in communication paths. This work proposes a fully decentralised algorithm (Epidemic K-Means) which does not require global communication and is intrinsically fault tolerant. The proposed distributed K-Means algorithm provides a clustering solution which can approximate the solution of an ideal centralised algorithm over the aggregated data as closely as desired. A comparative performance analysis is carried out against the state of the art distributed K-Means algorithms based on sampling methods. The experimental analysis confirms that the proposed algorithm is a practical and accurate distributed K-Means implementation for networked systems of very large and extreme scale.

Type 2 Design K Starboard Side

Print No: 76; Discontinued stamp SEP 18 1918

Study of W boson production in PbPb and pp collisions at root s(NN)=2.76 TeV

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Jet momentum dependence of jet quenching in PbPb collisions at root s(NN)=2.76 TeV

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Measurement of isolated photon production in pp and PbPb collisions at root s(NN)=2.76 TeV

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Study of Z Boson Production in PbPb Collisions at root s(NN)=2.76 TeV

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Indications of Suppression of Excited Upsilon States in Pb-Pb Collisions at root(NN)-N-s=2.76 TeV

A comparison of the relative yields of Upsilon resonances in the mu(+)mu(-) decay channel in Pb-Pb and pp collisions at a center-of-mass energy per nucleon pair of 2.76 TeV is performed with data collected with the CMS detector at the LHC. Using muons of transverse momentum above 4 GeV/c and pseudorapidity below 2.4, the double ratio of the Upsilon(2S) and Upsilon(3S) excited states to the Upsilon(1S) ground state in Pb-Pb and pp collisions, [Upsilon(2S + 3S)/Upsilon(1S)](Pb-Pb) /[Upsilon 2S + 3S)/Upsilon(1S)](pp), is found to be 0.31(-0.15)(+0.19) (stat_ +/- 0.03(syst). The probability to obtain the measured value, or lower, if the true double ratio is unity, is calculated to be less than 1%.