Because of its requirement for signaling by multiple cytokines, Janus kinase 3 (JAK3) is an excellent target for clinical immunosuppression. We report the development of a specific, orally active inhibitor of JAK3, CP-690,550, that significantly prolonged survival in a murine model of heart transplantation and in cynomolgus monkeys receiving kidney transplants. CP-690,550 treatment was not associated with hypertension, hyperlipidemia, or lymphoproliferative disease. On the basis of these preclinical results, we believe JAK3 blockade by CP-690,550 has potential for therapeutically desirable immunosuppression in human organ transplantation and in other clinical settings. 相似文献
Mass spectrometry data on plutonium isolated from Columbia River sediments exhibit mean ratios of plutonium-240 to plutonium-242 consistent with those observed for integrated global fallout. Ratios of plutonium-240 to plutonium-239 show marked deviations from accepted fallout values, suggesting a second source of plutonium-239. This additional plutonium-239 arises from the decay of neptunium-239 produced in reactor effluent water from the old plutonium production reactors located on the Hanford Reservation. An estimated 20 to 25 percent of the total plutonium inventory in sediments behind McNary Reservoir, the first downriver site of fine sediment accumulation below the Hanford Reservation, is ascribed to reactor operations. 相似文献
Late Cretaceous (Cenomanian) fossils discovered in the Kem Kem region of Morocco include large predatory dinosaurs that inhabited Africa as it drifted into geographic isolation. One, represented by a skull approximately 1.6 meters in length, is an advanced allosauroid referable to the African genus Carcharodontosaurus. Another, represented by a partial skeleton with slender proportions, is a new basal coelurosaur closely resembling the Egyptian genus Bahariasaurus. Comparisons with Cretaceous theropods from other continents reveal a previously unrecognized global radiation of carcharodontosaurid predators. Substantial geographic differentiation of dinosaurian faunas in response to continental drift appears to have arisen abruptly at the beginning of the Late Cretaceous. 相似文献
Serum chemistry analyses were compared between captive and free-ranging giraffes (Giraffa camelopardalis) in an attempt to better understand some of the medical issues seen with captive giraffes. Illnesses, including peracute mortality, energy malnutrition, pancreatic disease, urolithiasis, hoof disease, and severe intestinal parasitism, may be related to zoo nutrition and management issues. Serum samples were collected from 20 captive giraffes at 10 United States institutions. Thirteen of the captive animal samples were collected from animals trained for blood collection; seven were banked samples obtained from a previous serum collection. These samples were compared with serum samples collected from 24 free-ranging giraffes in South Africa. Differences between captive and free-ranging giraffes, males and females, and adults and subadults were analyzed by using a 2 x 2 x 2 factorial and Fisher's least significant difference for mean separation; when necessary variables were ranked and analyzed via analysis of variance. Potassium and bilirubin concentrations and alanine aminotransferase (ALT) activities were different between captive and free-ranging giraffes, but all fell within normal bovid reference ranges. The average glucose concentration was significantly elevated in free-ranging giraffes (161 mg/dl) compared with captive giraffes (113 mg/dl). All giraffes in this study had glucose concentrations higher than bovine (42-75 mg/ dl) and caprine (48-76 mg/dl) reference ranges. Differences were also seen in lipase, chloride, and magnesium though these findings are likely not clinically significant. There were no differences detected between sexes. Adults had higher concentrations of potassium, total protein, globulins, and chloride and higher gamma glutamyltransferase activities, whereas subadults had higher concentrations of phosphorus. Within the captive group, nonimmobilized animals had higher concentrations of total protein and globulins. Captive giraffe diets need further investigation to determine if the differences seen in this study, especially glucose and bilirubin concentrations and ALT activities, may result in some health problems often seen in captive giraffes. 相似文献
Historically, agriculturally induced CO2 release from soils has contributed to rising levels in the atmosphere. However, by using appropriate management, soils can be turned into carbon sinks. Many of the dryland regions of the world are characterised by degraded soils, a high incidence of poverty and a low capacity to invest in agriculture. Two well-proven soil organic matter models (CENTURY 4.0 and RothC-26 3) were used two explore the effects of modifying agricultural practices to increase soil carbon stocks. The changes to land management were chosen to avoid any significant increase in energy input whilst using technologies that would be available without radically altering the current agricultural methodology. Case studies were selected from dryland farming systems in Nigeria, Sudan and Argentina. Modelling showed that it would be possible to make alterations within the structure of the current farming systems to convert these soils from carbon sources to net sinks. Annual rates of carbon sequestration in the range 0.08–0.17 Mg ha−1 year−1 averaged over the next 50 years could be obtained. The most effective practices were those that maximised the input of organic matter, particularly farmyard manure (up to 0.09 Mg ha−1 year−1), maintaining trees (up to 0.15 Mg ha−1 year−1) and adopting zero tillage (up to 0.04 Mg ha−1 year−1). Verification of these predictions will require experimental data collected from field studies. 相似文献
Long- and short-term direct-drilling and seed broadcasting plus rotovation were examined as possible quick and cheap alternatives to conventional mouldboard ploughing and drilling. The experiment was the continuation of an existing long-term tillage experiment for spring barley. The conventional ploughing and long-term direct-drilling treatments continued on the same plots. The broadcasting and the short-term direct-drilling treatments were applied to previously chisel-ploughed and deep mouldboard-ploughed treatments, respectively. Autumn nitrogen treatments of 30 or 60 kg ha−1 and spring nitrogen treatments of 150 or 225 kg ha−1 were applied. The experiment is located on a cambisol (15% clay in topsoil) and on a gleysol (17% clay in topsoil) in south-east Scotland. Straw was removed by baling and the stubble remained when the treatments were applied.
Long-term direct-drilling yielded most over the 3 years of the experiment and was particularly successful after the unusually wet autumn and winter of the third season. Short-term direct-drilling was the lowest yielding treatment in the first season only. The success of the long-term direct-drilling treatment was associated with the development of a stable, protective surface tilth as a result of organic-matter accumulation. This was associated with some soil structural improvement deeper in the profile in the long-term direct-drilled gleysol as shown by measurements of air permeability. Crop performance apparently was not related to soil compactness or cone resistance. The relatively high rates of nitrogen applied, both autumn and spring, gave worthwhile crop responses except for the third season, when the crop lodged. Short-term direct-drilling, broadcasting with rotovation and ploughing with drilling gave similar average yields on the gleysol, but on the cambisol broadcasting with rotovation outyielded the other two treatments by an average of 0.3 t ha−1. 相似文献
Ovine vulvitis was experimentally reproduced by intravaginal inoculation of a mixture of bacterial strains of the histophilus/haemophilus group isolated from field cases. Grossly, the experimental vulvitis was identical to the field condition, and bacteria indistinguishable from the inoculated strains were reisolated. 相似文献