Palaeoenvironment and palaeoclimate of the Middle Miocene lake in the Steinheim basin, SW Germany: A reconstruction from C, O, and Sr isotopes of fossil remains

A differentiated reconstruction of palaeolimnologic, -environmental, and -climatic conditions is presented for the Middle Miocene long-term freshwater lake (14.3 to 13.5 Ma) of the Steinheim basin, on the basis of a combined C, 0, and Sr isotope study of sympatric skeletal fossils of aquatic and terrestrial organisms from the lake sediments. The oxygen isotope composition for lake water of the Steinheim basin (delta O-18(H2O) = +2.0 +/- 0.4 parts per thousand VSMOW, n = 6) was reconstructed from measurements of delta O-18(PO4) of aquatic turtle bones. The drinking water calculated from the enamel of large mammals (proboscideans, rhinocerotids, equids, cervids, suids) has delta O-18(H2O) values (delta(OH2O)-O-18 = -5.9 +/- 1.7 parts per thousand VSMOW, n = 31) typical for Middle Miocene meteoric water of the area. This delta O-18(H2O) value corresponds to a mean annual air temperature (MAT) of 18.8 +/- 3.8 degrees C, calculated using a modem-day delta(OH2O)-O-18-MAT relation. Hence, large mammals did not use the lake water as principal drinking water. In contrast, small mammals, especially the then abundant pika Prolagus oeningensis drank from O-18-enriched water sources (delta O-18(H2O) = +2.7 +/- 2.3 parts per thousand VSMOW, n = 7), such as the lake water. Differences in Sr and 0 isotopic compositions between large and small mammal teeth indicate different home ranges and drinking behaviour and support migration of some large mammals between the Swabian Alb plateau and the nearby Molasse basin, while small mammals ingested their food and water locally. Changes in the lake level, water chemistry, and temperature were inferred using isotopic compositions of ostracod and gastropod shells from a composite lake sediment profile. Calcitic ostracod valves (Ilyocypris binocularis; delta O-18 = +1.7 +/- 1.2 parts per thousand VPDB, delta C-18 = -0.5 +/- 0.9 parts per thousand, VPDB, n = 68) and aragonitic, gastropod shells (Gyraulus spp.; delta O-18 = +2.0 +/- 13 parts per thousand VPDB, delta C-13 = -1.1 +/- 1.3 parts per thousand VPDB, n = 89) have delta O-18 and delta C-13 values similar to or even higher than those of marine, carbonates. delta C-13 values:of the biogenic carbonates parallel lake level fluctuations while delta O-18 values scatter around +2 +/- 2 parts per thousand and reflect the short term variability of meteoric water inflow vs. longer term evaporation. Sr-87/Sr-86 ratios of aragonitic Gyraulus spp. gastropod shells parallel the lake level fluctuations, reflecting variable inputs of groundwater and surface waters. Using a water delta O-18(H2O) value of +2.0 parts per thousand VSMOW, water temperatures calculated from skeletal tissue delta O-18 values of ostracods are 16.7 +/- 5.0 degrees C, gastropods 20.6 +/- 5.6 degrees C, otoliths 21.8 +/- 1.4 degrees C, and fish teeth 17.0 +/- 2.7 degrees C. The calculated MAT (similar to 19 degrees C), lake water temperatures (similar to 17 to 22 degrees C) and the O-18-enriched water compositions are indicative of warm-temperate climatic conditions, possibly with a high humidity during this period. Vegetation in the area surrounding the basin was largely of the C-3-type, as indicated by carbon isotopic compositions of tooth enamel from large mammals (delta C-13 = -11.1 +/- 1.1 parts per thousand VPDB, n = 40). (c) 2006 Elsevier B.V. All rights reserved.

Intrauterine devices and endometrial cancer risk : a pooled analysis of the Epidemiology of Endometrial Cancer Consortium

Intrauterine devices (IUDs), long-acting and reversible contraceptives, induce a number of immunological and biochemical changes in the uterine environment that could affect endometrial cancer (EC) risk. We addressed this relationship through a pooled analysis of data collected in the Epidemiology of Endometrial Cancer Consortium. We combined individual-level data from 4 cohort and 14 case-control studies, in total 8,801 EC cases and 15,357 controls. Using multivariable logistic regression, we estimated pooled odds ratios (pooled-ORs) and 95% confidence intervals (CIs) for EC risk associated with ever use, type of device, ages at first and last use, duration of use and time since last use, stratified by study and adjusted for confounders. Ever use of IUDs was inversely related to EC risk (pooled-OR = 0.81, 95% CI = 0.74-0.90). Compared with never use, reduced risk of EC was observed for inert IUDs (pooled-OR = 0.69, 95% CI = 0.58-0.82), older age at first use (≥35 years pooled-OR = 0.53, 95% CI = 0.43-0.67), older age at last use (≥45 years pooled-OR = 0.60, 95% CI = 0.50-0.72), longer duration of use (≥10 years pooled-OR = 0.61, 95% CI = 0.52-0.71) and recent use (within 1 year of study entry pooled-OR = 0.39, 95% CI = 0.30-0.49). Future studies are needed to assess the respective roles of detection biases and biologic effects related to foreign body responses in the endometrium, heavier bleeding (and increased clearance of carcinogenic cells) and localized hormonal changes.

Open to closed system transition traced through the TDIC isotopic signature at the aquifer recharge stage, implications for groundwater 14C dating

14C dating models are limited when considering recent groundwater for which the carbon isotopic signature of the total dissolved inorganic carbon (TDIC) is mainly acquired in the unsaturated zone. Reducing the uncertainties of dating thus implies a better identification of the processes controlling the carbon isotopic composition of the TDIC during groundwater recharge. Geochemical interactions between gas, water and carbonates in the unsaturated zone were investigated for two aquifers (the carbonate-free Fontainebleau sands and carbonate-bearing Astian sands, France) in order to identify the respective roles of CO2 and carbonates on the carbon isotopic signatures of the TDIC; this analysis is usually approached using open or closed system terms. Under fully open system conditions, the seasonality of the 13C values in the soil CO2 can lead to important uncertainties regarding the so-called "initial 14C activity" used in 14C correction models. In a carbonate-bearing unsaturated zone such as in the Astian aquifer, we show that an approach based on fully open or closed system conditions is not appropriate. Although the chemical saturation between water and calcite occurs rapidly within the first metre of the unsaturated zone, the carbon isotopic contents (δ13C) of the CO2 and the TDIC evolve downward, impacted by the dissolution-precipitation of the carbonates. In this study, we propose a numerical approach to describe this evolution. The δ13C and the A 14C (radiocarbon activity) of the TDIC at the base of the carbonate-hearing unsaturated zone depends on (i) the δ13C and the A 14C of the TDIC in the soil determined by the soil CO2, (ii) the water's residence time in the unsaturated zone and (iii) the carbonate precipitation-dissolution fluxes. In this type of situation, the carbonate δ13C-A 14C evolutions indicate the presence of secondary calcite and permit the calculation of its accretion flux, equal to ~ 4.5 ± 0.5 x 10-9 mol grock-1 yr-1. More generally, for other sites under temperate climate and with similar properties to the Astian sands site, this approach allows for a reliable determination of the carbon isotopic composition at the base of the unsaturated zone as the indispensable "input function" data of the carbon cycle into the aquifer.

Decomposição e liberação de nitrogênio de resíduos culturais de plantas de cobertura de solo solteiras e consorciadas

A dinâmica de decomposição e liberação de nitrogênio (N) de resíduos culturais provenientes de plantas de cobertura de solo, solteiras e consorciadas, foi avaliada em um experimento realizado em condições de campo, utilizando-se os seguintes materiais: (a) aveia preta (Avena strigosa Schieb); (b) ervilhaca comum (Vicia sativa L.); (c) nabo forrageiro (Raphanus sativus L. var. oleiferus Metzg.); (d) 32 % de aveia preta + 68 % de ervilhaca comum, e (e) 51 % de aveia preta + 49 % de ervilhaca comum. Para monitorar o processo de decomposição, o material vegetal, seco ao ar, foi colocado em bolsas de nylon de 0,2 x 0,2 m e com malha de 0,5 mm, as quais foram deixadas na superfície do solo e recolhidas após 15, 29, 43, 59, 71, 82, 112 e 182 dias. Nos materiais coletados, foram feitas determinações das quantidades remanescentes de matéria seca (MS) e da sua concentração de N. Aos valores obtidos para as quantidades remanescentes de matéria seca e N, foram ajustados modelos não-lineares, com vistas em separar a MS e o N dos resíduos culturais em dois compartimentos, sendo um mais facilmente decomponível e outro mais recalcitrante. Dentre as espécies solteiras, a ervilhaca foi a que apresentou a maior taxa de decomposição (0,06119 dia-1) da MS do compartimento mais facilmente decomponível. A presença da aveia nos consórcios com ervilhaca reduziu em 30 % (0,04264 dia-1) e 50 % (0,03113 dia-1) a decomposição da MS desse compartimento, quando a proporção de matéria seca da gramínea foi de 32 e 51 %, respectivamente. Da quantidade total de N liberada durante os 182 dias do experimento, a maior parte ocorreu nos primeiros 15 dias. Os resultados deste estudo evidenciaram que, consorciando aveia e ervilhaca, não houve redução na taxa de liberação do N do compartimento mais facilmente mineralizável, em relação à ervilhaca solteira. No entanto, os resíduos culturais do consórcio entre aveia e ervilhaca apresentaram maior persistência no solo do que aqueles da ervilhaca solteira e liberaram maiores quantidades de N do que a aveia e o nabo solteiros.

Gas6 deficiency in recipient mice of allogeneic transplantation alleviates hepatic graft-versus-host disease.

Growth arrest-specific gene 6 (Gas6) is expressed in antigen-presenting cells and endothelial cells (ECs) but not in T cells. When wild-type (WT) or Gas6(-/-) mice received allogeneic non-T cell-depleted bone marrow cells, hepatic graft-versus-host disease (GVHD) was alleviated in Gas6(-/-) recipients regardless of donor genotype, but not in WT recipients. T-cell infiltration was more prominent and diffuse in WT than in Gas6(-/-) recipients' liver. When mice received 0.5 x 10(6) allogeneic T cells with T cell-depleted allogeneic bone marrow, clinical signs indicated that GVHD was less severe in Gas6(-/-) than in WT recipients, as shown by a significant improvement of the survival and reduced liver GVHD. These data demonstrate that donor cells were not involved in the protection mechanism. In addition, lack of Gas6 in antigen-presenting cells did not affect WT or Gas6(-/-) T-cell proliferation. We therefore assessed the response of WT or Gas6(-/-) ECs to tumor necrosis factor-alpha. Lymphocyte transmigration was less extensive through Gas6(-/-) than WT ECs and was not accompanied by increases in adhesion molecule levels. Thus, the lack of Gas6 in ECs impaired donor T-cell transmigration into the liver, providing a rationale for considering Gas6 pathway as a potential nonimmunosuppressive target to minimize GVHD in patients receiving allogeneic hematopoietic stem cell transplantation.

Quantificação da resistência tênsil e da friabilidade de um latossolo vermelho distroférrico sob plantio direto

A qualidade estrutural do solo é importante para a emergência das plântulas, bem como para o crescimento, desenvolvimento e produtividade das culturas. Uma ampla distribuição de valores de resistência tênsil do solo indica condições estruturais do solo para atender a estes pressupostos. O objetivo deste trabalho foi avaliar a resistência tênsil e a friabilidade de um Latossolo Vermelho distroférrico sob plantio direto com sucessão e rotação de culturas. Os tratamentos utilizados foram: plantio direto com sucessão das culturas de trigo e soja (SDS); plantio direto com rotação de culturas, utilizando em seqüência milho-aveia-soja-aveia-soja-trigo (SDR), e SDR associado à escarificação periódica do solo (SDE). Em duas épocas distintas (outubro de 2003 e abril de 2004), foram coletados dez blocos de solo (0,15 x 0,20 x 0,10 m) em cada tratamento na camada de 0-0,20 m de profundidade. Quatrocentos e cinqüenta agregados de cada tratamento e época de coleta foram utilizados para determinar a resistência tênsil e a friabilidade do solo, determinando-se, também, o conteúdo de C orgânico. Não foi verificada influência do C orgânico do solo na resistência tênsil e na friabilidade do solo. Verificou-se menor resistência tênsil em SDE para o ano de 2003. A sucessão de culturas (SDS) alternou temporariamente a friabilidade do solo entre a classe friável e a muito friável. A rotação de culturas (SDR) manteve temporalmente estável a estrutura do solo na classe de friabilidade do solo muito friável, assegurando melhor estrutura e qualidade física do solo. A resistência tênsil dos agregados e a friabilidade foram sensíveis na avaliação da qualidade estrutural do solo para os sistemas de manejo de solo e culturas estudados.

Climate oscillations and species interactions: large-scale congruence but regional differences in the phylogeographic structures of an alpine plant and its monophagous insect

Aim. To predict the fate of alpine interactions involving specialized species, using a monophagous beetle and its host-plant as a case study. Location. The Alps. Methods. We investigated genetic structuring of the herbivorous beetle Oreina gloriosa and its specific host-plant Peucedanum ostruthium. We used genome fingerprinting (in the insect and the plant) and sequence data (in the insect) to compare the distribution of the main gene pools in the two associated species and to estimate divergence time in the insect, a proxy for the temporal origin of the interaction. We quantified the similarity in spatial genetic structures by performing a Procrustes analysis, a tool from the shape theory. Finally, we simulated recolonization of an empty space analogous to the deglaciated Alps just after ice retreat by two lineages from two species showing unbalanced dependence, to examine how timing of the recolonization process, as well as dispersal capacities of associated species, could explain the observed pattern. Results. Contrasting with expectations based on their asymmetrical dependence, patterns in the beetle and plant were congruent at a large scale. Exceptions occurred at a regional scale in areas of admixture, matching known suture zones in Alpine plants. Simulations using a lattice-based model suggested these empirical patterns arose during or soon after recolonization, long after the estimated origin of the interaction c. 0.5 million years ago. Main conclusions. Species-specific interactions are scarce in alpine habitats because glacial cycles have limited opportunities for coevolution. Their fate, however, remains uncertain under climate change. Here we show that whereas most dispersal routes are paralleled at large scale, regional incongruence implies that the destinies of the species might differ under changing climate. This may be a consequence of the host-dependence of the beetle that locally limits the establishment of dispersing insects.

Atomic diffusion induced by stress relaxation in InGaAs/GaAs epitaxial layers

The origin of the microscopic inhomogeneities in InxGa12xAs layers grown on GaAs by molecular beam epitaxy is analyzed through the optical absorption spectra near the band gap. It is seen that, for relaxed thick layers of about 2.8 mm, composition inhomogeneities are responsible for the band edge smoothing into the whole compositional range (0.05,x,0.8). On the other hand, in thin enough layers strain inhomogeneities are dominant. This evolution in line with layer thickness is due to the atomic diffusion at the surface during growth, induced by the strain inhomogeneities that arise from stress relaxation. In consequence, the strain variations present in the layer are converted into composition variations during growth. This process is energetically favorable as it diminishes elastic energy. An additional support to this hypothesis is given by a clear proportionality between the magnitude of the composition variations and the mean strain.

Determination of the direct band-gap energy of InAlAs matched to InP by photoluminescence excitation spectroscopy

A series of InxAl12xAs samples (0.51,x,0.55) coherently grown on InP was studied in order to measure the band-gap energy of the lattice matched composition. As the substrate is opaque to the relevant photon energies, a method is developed to calculate the optical absorption coefficient from the photoluminescence excitation spectra. The effect of strain on the band-gap energy has been taken into account. For x50.532, at 14 K we have obtained Eg05154966 meV. © 1997 American Institute of Physics.

Liberação de macronutrientes das palhadas de milheto solteiro e consorciado com feijão-de-porco sob cultivo de feijão

A ciclagem de nutrientes está relacionada com a capacidade de absorção das diferentes espécies de plantas de cobertura. Já as velocidades de decomposição e liberação de nutrientes, das palhadas produzidas pelas mesmas, têm com fator principal a relação C/N, com diferença marcante entre gramíneas e leguminosas. Neste sentido, o objetivo deste trabalho foi avaliar a produção de matéria seca, teor, acúmulo, decomposição e liberação de macronutrientes da palhada de milheto (Pennisetum typhoides (Burm.) Stapf) solteiro e consorciado com feijão-de-porco (Canavalia ensiformes (L.) DC.), em ambiente de campo, sob a cultura do feijoeiro, semeada em agosto de 2005 (inverno/primavera), em um Latossolo Vermelho distroférrico típico. A liberação de nutrientes foi determinada por meio da distribuição de bolsas confeccionadas com telas de náilon, com malha de 1 mm, de dimensões de 0,2 x 0,2 m, preenchidas com quantidades de palha proporcionais à área da bolsa. O delineamento utilizado foi o de blocos casualizados, com quatro repetições, em esquema de parcelas subdivididas. As parcelas foram constituídas pelos dois tipos de palhadas (milheto e milheto + feijão-de-porco), e as subparcelas, pelas épocas de avaliação ao longo do cultivo do feijoeiro (0, 8, 16, 24, 40, 56 e 72 dias após o manejo das plantas de cobertura). Os resíduos coletados foram secos em estufa de circulação forçada de ar, a 65 ºC, até atingirem peso constante, para determinação da matéria seca remanescente, sendo posteriormente moídos e encaminhados para a determinação dos teores de macronutrientes. Com base nos teores e na matéria seca remanescente, foram calculadas as quantidades remanescentes dos macronutrientes, sendo elas expressas em percentagem do valor inicial. Os valores foram ajustados a modelos não lineares, escolhendo-se aqueles com melhor ajuste em cada situação. A palhada de milheto + feijão-deporco apresentou maior quantidade de matéria seca e maiores teores de N e Ca, ciclando maior quantidade de todos os macronutrientes. A palhada de milheto + feijão-de-porco apresentou maiores velocidades de decomposição e liberação de N, Ca e Mg.

Numerical signs fos a transition in the 2d Random Field Ising Model at T=0

Intensive numerical studies of exact ground states of the two-dimensional ferromagnetic random field Ising model at T=0, with a Gaussian distribution of fields, are presented. Standard finite size scaling analysis of the data suggests the existence of a transition at ¿c=0.64±0.08. Results are compared with existing theories and with the study of metastable avalanches in the same model.

Composição lignocelulósica e isótopica da vegetação e da matéria orgânica do solo de uma turfeira tropical: I - composição florística, fitomassa e acúmulo de carbono

A matéria orgânica do solo (MOS) é um dos grandes reservatórios de carbono (C) da Terra e constitui um dos principais componentes do ciclo do C. Turfeiras, ambientes acumuladores de MOS, são produto da decomposição de vegetais, que se desenvolvem e se acumulam em ambientes saturados com água, sendo o estádio inicial da sequência de carbonificação. A fitomassa participa de forma marcante no ciclo global do C, armazenando em torno de 85 % de todo o C terrestre acima do solo. O tecido vegetal é composto principalmente por lignina, celulose e hemicelulose, constituindo até 85 % da biomassa seca. As plantas discriminam C de forma diferenciada, em razão de seu ciclo fotossintético (C3, C4 e CAM). As turfeiras da Serra do Espinhaço Meridional (SdEM-MG) são colonizadas por vegetação de Campo Limpo Úmido (CLU) e de Floresta Estacional Semidecidual (FES), onde ocorrem espécies dos ciclos fotossintéticos C3 e C4. Este trabalho objetivou avaliar a contribuição dessas duas fitofisionomias para o acúmulo de MOS, por meio da avaliação da fitomassa e da composição lignocelulósica e isotópica da vegetação e da MOS. A turfeira estudada localiza-se na SdEM e ocupa 81,75 ha. Para a estimativa da fitomassa do CLU e da FES, foram marcadas três parcelas de 0,5 x 0,5 m em cada fitofisionomia, onde todos os indivíduos da parcela foram cortados e armazenados. Para as análises isotópicas e lignocelulósicas da vegetação, identificaram-se as espécies dominantes em cada fitofisionomia. Amostras de solo foram coletadas em três locais representativos sob cada fitofisionomia, a cada 5 cm de profundidade, até 50 cm. Foram extraídas a celulose e a lignina das folhas das 15 espécies dominantes e das 60 amostras de turfeira para quantificação e determinação dos valores de δ13C e δ15N. Para datação da MOS, o 14C foi determinado em três profundidades, sob o CLU e a FES. A produção da fitomassa da FES foi muito superior à produção da do CLU. Os sinais isotópicos e a composição lignocelulósica da vegetação e da matéria orgânica do solo evidenciaram que a turfeira foi formada pela deposição de matéria orgânica da vegetação que a coloniza. O crescimento vertical e a taxa de acúmulo de C foram muito mais elevados sob a FES do que sob o CLU.

Common variants near MC4R are associated with fat mass, weight and risk of obesity.

To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits.

Interactions of dietary whole-grain intake with fasting glucose- and insulin-related genetic loci in individuals of European descent: a meta-analysis of 14 cohort studies.

Whole-grain foods are touted for multiple health benefits, including enhancing insulin sensitivity and reducing type 2 diabetes risk. Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) associated with fasting glucose and insulin concentrations in individuals free of diabetes. We tested the hypothesis that whole-grain food intake and genetic variation interact to influence concentrations of fasting glucose and insulin. Via meta-analysis of data from 14 cohorts comprising ∼ 48,000 participants of European descent, we studied interactions of whole-grain intake with loci previously associated in GWAS with fasting glucose (16 loci) and/or insulin (2 loci) concentrations. For tests of interaction, we considered a P value <0.0028 (0.05 of 18 tests) as statistically significant. Greater whole-grain food intake was associated with lower fasting glucose and insulin concentrations independent of demographics, other dietary and lifestyle factors, and BMI (β [95% CI] per 1-serving-greater whole-grain intake: -0.009 mmol/l glucose [-0.013 to -0.005], P < 0.0001 and -0.011 pmol/l [ln] insulin [-0.015 to -0.007], P = 0.0003). No interactions met our multiple testing-adjusted statistical significance threshold. The strongest SNP interaction with whole-grain intake was rs780094 (GCKR) for fasting insulin (P = 0.006), where greater whole-grain intake was associated with a smaller reduction in fasting insulin concentrations in those with the insulin-raising allele. Our results support the favorable association of whole-grain intake with fasting glucose and insulin and suggest a potential interaction between variation in GCKR and whole-grain intake in influencing fasting insulin concentrations.

Effects of erythropoietin on muscle O2 transport during exercise in patients with chronic renal failure.

Erythropoietin (rHuEPO) has proven to be effective in the treatment of anemia of chronic renal failure (CRF). Despite improving the quality of life, peak oxygen uptake after rHuEPO therapy is not improved as much as the increase in hemoglobin concentration ([Hb)] would predict. We hypothesized that this discrepancy is due to failure of O2 transport rates to rise in a manner proportional to [Hb]. To test this, eight patients with CRF undergoing regular hemodialysis were studied pre- and post-rHuEPO ([Hb] = 7.5 +/- 1.0 vs. 12.5 +/- 1.0 g x dl-1) using a standard incremental cycle exercise protocol. A group of 12 healthy sedentary subjects of similar age and anthropometric characteristics served as controls. Arterial and femoral venous blood gas data were obtained and coupled with simultaneous measurements of femoral venous blood flow (Qleg) by thermodilution to obtain O2 delivery and oxygen uptake (VO2). Despite a 68% increase in [Hb], peak VO2 increased by only 33%. This could be explained largely by reduced peak leg blood flow, limiting the gain in O2 delivery to 37%. At peak VO2, after rHuEPO, O2 supply limitation of maximal VO2 was found to occur, permitting the calculation of a value for muscle O2 conductance from capillary to mitochondria (DO2). While DO2 was slightly improved after rHuEPO, it was only 67% of that of sedentary control subjects. This kept maximal oxygen extraction at only 70%. Two important conclusions can be reached from this study. First, the increase in [Hb] produced by rHuEPO is accompanied by a significant reduction in peak blood flow to exercising muscle, which limits the gain in oxygen transport. Second, even after restoration of [Hb], O2 conductance from the muscle capillary to the mitochondria remains considerably below normal.