Acoustic emissions from spin crossover complexes.

Acoustic emission from the compounds [Fe(HB(tz)3)2] and [Fe(Htrz)(trz)2]BF4 was detected during the thermally induced spin transition and is correlated with simultaneously recorded calorimetric signals. We ascribe this phenomenon to elastic waves produced by microstructural and volume changes accompanying the spin transition. Despite the perfect reversibility of the spin state switching (seen by the calorimeter), the acoustic emission activity decreases for successive thermal cycles, revealing thus irreversible microstructural evolution of the samples. The acoustic emission signal amplitude and energy probability distribution functions followed power-law behavior and the characteristic exponents were found to be similar for the two samples both on heating and cooling, indicating the universal character, which is further substantiated by the well scaled average temporal shapes of the avalanches.

Host space, not energy or symbiont size, constrains feather mite abundance across passerine bird species.

Comprehending symbiont abundance among host species is a major ecological endeavour, and the metabolic theory of ecology has been proposed to understand what constrains symbiont populations. We parameterized metabolic theory equations to investigate how bird species' body size and the body size of their feather mites relate to mite abundance according to four potential energy (uropygial gland size) and space constraints (wing area, total length of barbs and number of feather barbs). Predictions were compared with the empirical scaling of feather mite abundance across 106 passerine bird species (26,604 individual birds sampled), using phylogenetic modelling and quantile regression. Feather mite abundance was strongly constrained by host space (number of feather barbs) but not by energy. Moreover, feather mite species' body size was unrelated to the body size of their host species. We discuss the implications of our results for our understanding of the bird-feather mite system and for symbiont abundance in general.

3D Reconstruction of the Blood Supply in an Elephant's Forefoot Using Fused CT and MRI Sequences.

Being the largest still-living terrestrial mammal on earth, an elephant's feet play an important role in its health status. The musculoskeletal structures in the forefoot are well described in the literature, but information about vascularization is limited. The novel aim of this work is to provide anatomical guidance to structures found in the forefoot, focusing on the arterial system. Initially, native CT and MRI sequences were taken of the left forefoot of a deceased 6-year-old female Asian elephant; the foot was then filled with an iodine-containing contrast medium through the a. mediana and the CT scans were repeated in the same position. The images obtained were processed with 3D Slicer software for the 3D reconstruction of the bones and arteries. The results clearly showed the palmar blood supply of the forefoot. A so far undescribed vessel was revealed, stemming from the a. metacarpea, supplying the first digit and the digital cushion. The course of the deep palmar arch's terminal section was also established. This paper provides the first description of the exact disposition of the arteries in the palmar aspect of an elephant's forefoot and may be used in planning surgeries in clinically affected animals.

Towards the Big History of information. Approaching the origins of information behaviour.

A palaeontological analysis of the evolutionary steps of Metazoa is tracing back the appearance and first steps of information behaviour as far as the Proterozoic Eon. Either the neural cell or the nervous system or the eyesight did not trigger the appearance of the information behaviour, but it did a novel way of diet. Carnivorous diet appeared on Earth slightly before the information behaviour as a completely new way of feeding - and what is more important: the application of light into the behavioural complexes as a radically innovative survival supporting tool. A genetic toolkit was ready for Metazoa, and the combination of the neural system, eyesight and carnivorous diet initiated the information behaviour. We provide an answer for this simple question: why did the carnivorous diet result in the first disruptive innovation in information behaviour? The junction of Big History, palaeontology and information history provides many challenging new aspects for further research.

Scaling of Average Avalanche Shapes for Acoustic Emission during Jerky Motion of Single Twin Boundary in Single-Crystalline Ni2MnGa.

Temporal average shapes of crackling noise avalanches, U(t) (U is the detected parameter proportional to the interface velocity), have self-similar behavior, and it is expected that by appropriate normalization, they can be scaled together according to a universal scaling function. There are also universal scaling relations between the avalanche parameters (amplitude, A, energy, E, size (area), S, and duration, T), which in the mean field theory (MFT) have the form E∝A3, S∝A2, S∝T2. Recently, it turned out that normalizing the theoretically predicted average U(t) function at a fixed size, U(t)=atexp-bt2 (a and b are non-universal, material-dependent constants) by A and the rising time, R, a universal function can be obtained for acoustic emission (AE) avalanches emitted during interface motions in martensitic transformations, using the relation R~A1-φ too, where φ is a mechanism-dependent constant. It was shown that φ also appears in the scaling relations E~A3-φ and S~A2-φ, in accordance with the enigma for AE, that the above exponents are close to 2 and 1, respectively (in the MFT limit, i.e., with φ= 0, they are 3 and 2, respectively). In this paper, we analyze these properties for acoustic emission measurements carried out during the jerky motion of a single twin boundary in a Ni50Mn28.5Ga21.5 single crystal during slow compression. We show that calculating from the above-mentioned relations and normalizing the time axis of the average avalanche shapes with A1-φ, and the voltage axis with A, the averaged avalanche shapes for the fixed area are well scaled together for different size ranges. These have similar universal shapes as those obtained for the intermittent motion of austenite/martensite interfaces in two different shape memory alloys. The averaged shapes for a fixed duration, although they could be acceptably scaled together, showed a strong positive asymmetry (the avalanches decelerate much slower than they accelerate) and thus did not show a shape reminiscent of an inverted parabola, predicted by the MFT. For comparison, the above scaling exponents were also calculated from simultaneously measured magnetic emission data. It was obtained that the φ values are in accordance with theoretical predictions going beyond the MFT, but the AE results for φ are characteristically different from these, supporting that the well-known enigma for AE is related to this deviation.

Thermodynamic Analysis of Anomalous Shape of Stress-Strain Curves for Shape Memory Alloys.

In some shape-memory single crystals the stress-strain (σ~ε) curves, belonging to stress induced martensitic transformations from austenite to martensite at fixed temperature, instead of being the usual slightly increasing function or horizontal, have an overall negative slope with sudden stress drops in it. We discuss this phenomenon by using a local equilibrium thermodynamic approach and analysing the sign of the second derivative of the difference of the Gibbs free energy. We show that, considering also the possible nucleation and growth of two martensite structural modifications/variants, the stress-strain loops can be unstable. This means that the overall slope of the uploading branch of the stress-strain curve can be negative for smooth transformation if the second martensite, which is more stable with larger transformation strain, is the final product. We also show that local stress-drops on the stress-strain curve can appear if the nucleation of the second martensite is difficult, and the presence of such local stress-drops alone can also result in an overall negative slope of the stress-strain curves. It is illustrated that the increase of the temperature of the thermal recovery during burst-like transition is a measure of the change of the nucleation energy: the more stable martensite has larger nucleation energy.

The little-known history of cleanliness and the forgotten pioneers of handwashing.

Handwashing is a simple method for preventing the spread of pathogens. It is now common practice, but this was not always the case. Advocating for it often costed a doctor his career in the 1840s. Hospitals in the early 1800s had little idea of the significance of hygiene; thus, they were often mocked as disease-producing incubators or as "houses of death." Many of the ill and dying were kept on wards with no ventilation or access to clean water; hospitals were found to offer only the most basic care. The mortality rate for patients admitted to hospital was three to five times greater than that for individuals cared for at home. Doctors did not routinely wash their hands until the mid-1800s, and they would proceed straight from dissecting a corpse to delivering a baby, providing the basis for the spread of puerperal fever. Despite advances in modern medicine, healthcare providers still face the issue of infection outbreaks caused by patient care. While the body of scientific data supporting hand hygiene as the key strategy to prevent the spread of pathogens is substantial, we highlight that achieving this crucial, long-awaited breakthrough was a hard task through history.

Clustering Characterization of Acoustic Emission Signals Belonging to Twinning and Dislocation Slip during Plastic Deformation of Polycrystalline Sn.

Results of acoustic emission (AE) measurements, carried out during plastic deformation of polycrystalline Sn samples, are analyzed by the adaptive sequential k-means method. The acoustic avalanches, originating from different sources, are separated on the basis of their spectral properties, that is, sorted into clusters, presented both on the so-called feature space (energy-median frequency plot) and on the power spectral density (PSD) curves. We found that one cluster in every measurement belongs to background vibrations, while the remaining ones are clearly attributed to twinning as well as dislocation slips at −30 °C and 25 °C, respectively. Interestingly, fingerprints of the well-known "ringing" of AE signals are present in different weights on the PSD curves. The energy and size distributions of the avalanches, corresponding to twinning and dislocation slips, show a bit different power-law exponents from those obtained earlier by fitting all AE signals without cluster separation. The maximum-likelihood estimation of the avalanche energy (ε) and size (τ) exponents provide ε=1.57±0.05 (at −30 °C) and ε=1.35±0.1 (at 25 °C), as well as τ=1.92±0.05 (at −30 °C) and τ= 1.55±0.1 (at 25 °C). The clustering analysis provides not only a manner to eliminate the background noise, but the characteristic avalanche shapes are also different for the two mechanisms, as it is visible on the PSD curves. Thus, we have illustrated that this clustering analysis is very useful in discriminating between different AE sources and can provide more realistic estimates, for example, for the characteristic exponents as compared to the classical hit-based approach where the exponents reflect an average value, containing hits from the low-frequency mechanical vibrations of the test machine, too.

Denouement of the Energy-Amplitude and Size-Amplitude Enigma for Acoustic-Emission Investigations of Materials.

There are many systems producing crackling noise (avalanches) in materials. Temporal shapes of avalanches, U(t) (U is the detected voltage signal, t is the time), have self-similar behaviour and the normalized U(t) function (e.g., dividing both the values of U and t by S1/2, where S is the avalanche area), averaged for fixed S, should be the same, independently of the type of materials or avalanche mechanisms. However, there are experimental evidences that the temporal shapes of avalanches do not scale completely in a universal way. The self-similarity also leads to universal power-law-scaling relations, e.g., between the energy, E, and the peak amplitude, Am, or between S and Am. There are well-known enigmas, where the above exponents in acoustic emission measurements are rather close to 2 and 1, respectively, instead of E~Am3 and S~Am2, obtained from the mean field theory, MFT. We show, using a theoretically predicted averaged function for the fixed avalanche area, U(t)=atexp(-bt2) (where a and b are non-universal, material-dependent constants), that the scaling exponents can be different from the MFT values. Normalizing U by Am and t by tm (the time belonging to the Am: rise time), we obtain tm~Am1-φ (the MFT values can be obtained only if φ would be zero). Here, φ is expected to be material-independent and to be the same for the same mechanism. Using experimental results on martensitic transformations in two different shape-memory single-crystals, φ = 0.8 ± 0.1 was obtained (φ is the same for both alloys). Thus, dividing U by Am as well as t by Am1-φ (~tm) leads to the same common, normalized temporal shape for different, fixed values of S. This normalization can also be used in general for other experimental results (not only for acoustic emission), which provide information about jerky noises in materials.

High frequency of social polygyny reveals little costs for females in a songbird.

Mating system theory predicts that social polygyny-when one male forms pair bonds with two females-may evolve by female choice in species with biparental care. Females will accept a polygynous male if the benefit of mating with a male providing high-quality genes or rearing resources outweighs the cost of sharing mate assistance in parental care. Based on this rationale, we hypothesise that the population frequency of social polygyny (FSP) varies due to changes in mate sharing costs caused by changing environmental conditions. We predicted that: (1) polygamous females (i.e. mated with a polygynous male) pay a survival cost compared to monogamous females; (2) FSP would be higher in years with better rearing conditions and (3) the difference in survival rates between monogamous and polygamous females would be small following years with higher FSP. We tested these predictions using regression and multistate analyses of capture-recapture data of pied flycatchers, Ficedula hypoleuca, in central Spain collected over 26 years (1990-2016). Monogamous females had a higher mean survival rate than polygamous females (prediction 1), but there was no difference in survival between polygynous and monogamous males. In addition, FSP was positively associated with annual reproductive success (a proxy of the quality of rearing conditions-prediction 2). Finally, following years with high FSP, the survival of polygamous females was similar to that of monogamous females (prediction 3), while the chance of breeding in a polygamous state for 2 years in a row increased for both males and females. Our findings suggest that fluctuating environmental conditions may be a necessary but neglected aspect of understanding social polygyny mechanisms.

Disturbance induced dynamics of a tritrophic novel ecosystem.

Novel ecosystems formed by invasive plants provide a good opportunity to get insight into early dynamics and pattern formation of these ecosystems. The invasive black locust as host plant, Bruchophagus robiniae as host-specific seed predator and its parasitoids were the components of the studied tritrophic system. To investigate disturbance-driven dynamics of this system we created seed-vacated host plant patches in a field experiment. We removed all pods from selected patches of black locust resulting in an induced local extinction of seed predators and their parasitoids. We hypothesized that disturbance enhances top-down control by parasitoids; this enhanced top-down control decreases seed predation, facilitating the host plant's spread. We found that disturbance modified only parasitism after controlling with year effect: in vacated patches median parasitism was higher than in control patches. Seed predation exceeded its initial level in vacated patches in the third year after the disturbance, but in the fourth year it dropped again presumably due to the strong top-down control. Our findings also suggested that the seed predator was also affected by the bottom-up control of its host plant's density. We found that in the studied new ecosystem the top-down control was strengthened by the disturbance. Since the host plant of the tritrophic system is an invasive species, partial habitat disturbance of such species may increase the severity of parasitoid top-down control, which may reduce seed predation by the herbivores.

Linear relationship found by magnetic resonance imaging between cerebrospinal fluid volume and body weight in dogs.

Despite numerous studies on cerebrospinal fluid (CSF) and its importance during hydrocephalus or myelography, no reliable values exist about its overall volume in dogs. In this study, our aim was to measure the intracranial (IC) volume of CSF in dogs and assess its possible relationship with body size and the symmetry of the lateral ventricles. We ran a 3D magnetic resonance imaging (MRI) sequence on the central nervous system of 12 healthy, male mongrel dogs between 3-5 years of age and 7.5-35.0 kg body weight. A validated semiautomatic segmentation protocol was implemented to segment the CSF and measure its volume. Values for the volume of the ventricular compartment were between 0.97 and 2.94 ml, with 62.1 ± 11.7% in the lateral ventricles, 17.6 ± 4.9% in the third ventricle, 4.9 ± 1.6% in the aqueductus mesencephali and 15.5 ± 6.6% in the fourth ventricle. In 11 cases a significant asymmetry was found between the lateral ventricles. The results suggest that it may be normal for a dog to have one of the lateral ventricles 1.5 times larger than the other. The correlation between body weight and CSF volume was linear, indicating that the current dosage protocols for myelography, based on a hypothetical proportional relationship with body weight, may have to be revised.

Linked selection and recombination rate variation drive the evolution of the genomic landscape of differentiation across the speciation continuum of Ficedula flycatchers.

Speciation is a continuous process during which genetic changes gradually accumulate in the genomes of diverging species. Recent studies have documented highly heterogeneous differentiation landscapes, with distinct regions of elevated differentiation ("differentiation islands") widespread across genomes. However, it remains unclear which processes drive the evolution of differentiation islands; how the differentiation landscape evolves as speciation advances; and ultimately, how differentiation islands are related to speciation. Here, we addressed these questions based on population genetic analyses of 200 resequenced genomes from 10 populations of four Ficedula flycatcher sister species. We show that a heterogeneous differentiation landscape starts emerging among populations within species, and differentiation islands evolve recurrently in the very same genomic regions among independent lineages. Contrary to expectations from models that interpret differentiation islands as genomic regions involved in reproductive isolation that are shielded from gene flow, patterns of sequence divergence (d(xy) and relative node depth) do not support a major role of gene flow in the evolution of the differentiation landscape in these species. Instead, as predicted by models of linked selection, genome-wide variation in diversity and differentiation can be explained by variation in recombination rate and the density of targets for selection. We thus conclude that the heterogeneous landscape of differentiation in Ficedula flycatchers evolves mainly as the result of background selection and selective sweeps in genomic regions of low recombination. Our results emphasize the necessity of incorporating linked selection as a null model to identify genome regions involved in adaptation and speciation.

COMPARISON BETWEEN MAGNETIC RESONANCE IMAGING ESTIMATES OF EXTRACRANIAL CEREBROSPINAL FLUID VOLUME AND PHYSICAL MEASUREMENTS IN HEALTHY DOGS.

Dosages for myelography procedures in dogs are based on a hypothetical proportional relationship between bodyweight and cerebrospinal fluid (CSF) volume. Anecdotal radiographic evidence and recent studies have challenged the existence of such a defined relationship in dogs. The objectives of this prospective cross-sectional study were to describe CSF volumes using magnetic resonance imaging (MRI) in a group of clinically healthy dogs, measure the accuracy of MRI CSF volumes, and compare MRI CSF volumes with dog physical measurements. A sampling perfection with application optimized contrast using different flip-angle evolution MRI examination of the central nervous system was carried out on 12 healthy, male mongrel dogs, aged between 3 and 5 years with a bodyweight range of 7.5-35.0 kg. The images were processed with image analysis freeware (3D Slicer) in order to calculate the volume of extracranial CSF. Cylindrical phantoms of known volume were included in scans and used to calculate accuracy of MRI volume estimates. The accuracy of MRI volume estimates was 99.8%. Extracranial compartment CSF volumes ranged from 20.21 to 44.06 ml. Overall volume of the extracranial CSF increased linearly with bodyweight, but the proportional volume (ml/bodyweight kilograms) of the extracranial CSF was inversely proportional to bodyweight. Relative ratios of volumes in the cervical, thoracic, and lumbosacral regions were constant. Findings indicated that the current standard method of using body weight to calculate dosages of myelographic contrast agents in dogs may need to be revised.

Evolutionary analysis of the female-specific avian W chromosome.

The typically repetitive nature of the sex-limited chromosome means that it is often excluded from or poorly covered in genome assemblies, hindering studies of evolutionary and population genomic processes in non-recombining chromosomes. Here, we present a draft assembly of the non-recombining region of the collared flycatcher W chromosome, containing 46 genes without evidence of female-specific functional differentiation. Survival of genes during W chromosome degeneration has been highly non-random and expression data suggest that this can be attributed to selection for maintaining gene dose and ancestral expression levels of essential genes. Re-sequencing of large population samples revealed dramatically reduced levels of within-species diversity and elevated rates of between-species differentiation (lineage sorting), consistent with low effective population size. Concordance between W chromosome and mitochondrial DNA phylogenetic trees demonstrates evolutionary stable matrilineal inheritance of this nuclear-cytonuclear pair of chromosomes. Our results show both commonalities and differences between W chromosome and Y chromosome evolution.

Using the BirdTree.org website to obtain robust phylogenies for avian comparative studies: A primer.

Comparative studies of trait evolution require accounting for the shared evolutionary history. This is done by including phylogenetic hypotheses into statistical analyses of species' traits, for which birds often serve as excellent models. The online publication of the most complete molecular phylogeny of extant bird species (www.birdtree.org, BirdTree hereafter) now allows evolutionary biologists to rapidly obtain sets of equally plausible phylogenetic trees for any set of species to be incorporated as a phylogenetic hypothesis in comparative analyses. We discuss methods to use BirdTree tree sets for comparative studies, either by building a consensus tree that can be incorporated into standard comparative analyses, or by using tree sets to account for the effect of phylogenetic uncertainty. Methods accounting for phylogenetic uncertainty should be preferred whenever possible because they should provide more reliable parameter estimates and realistic confidence intervals around them. Based on a real comparative dataset, we ran simulations to investigate the effect of variation in the size of the random tree sets downloaded from BirdTree on the variability of parameter estimates from a bivariate relationship between mass-specific productivity and body mass. Irrespective of the method of analysis, using at least 1,000 trees allows obtaining parameter estimates with very small (< 0.15%) coefficients of variation. We argue that BirdTree, due to the ease of use and the major advantages over previous 'traditional' methods to obtain phylogenetic hypotheses of bird species (e.g. supertrees or manual coding of published phylogenies), will become the standard reference in avian comparative studies for years to come.

No personality without experience? A test on Rana dalmatina tadpoles.

While the number of studies reporting the presence of individual behavioral consistency (animal personality, behavioral syndrome) has boomed in the recent years, there is still much controversy about the proximate and ultimate mechanisms resulting in the phenomenon. For instance, direct environmental effects during ontogeny (phenotypic plasticity) as the proximate mechanism behind the emergence of consistent individual differences in behavior are usually overlooked compared to environmental effects operating across generations (genetic adaptation). Here, we tested the effects of sociality and perceived predation risk during ontogeny on the strength of behavioral consistency in agile frog (Rana dalmatina) tadpoles in a factorial common garden experiment. Tadpoles reared alone and without predatory cues showed zero repeatability within (i.e., lack of personality) and zero correlation between (i.e., lack of syndrome) activity and risk-taking. On the other hand, cues from predators alone induced both activity and risk-taking personalities, while cues from predators and conspecifics together resulted in an activity - risk-taking behavioral syndrome. Our results show that individual experience has an unequivocal role in the emergence of behavioral consistency. In this particular case, the development of behavioral consistency was most likely the result of genotype × environment interactions, or with other words, individual variation in behavioral plasticity.

The relationship between DRD4 polymorphisms and phenotypic correlations of behaviors in the collared flycatcher.

There is increasing evidence that the genetic architecture of exploration behavior includes the dopamine receptor D4 gene (DRD4). Such a link implies that the within-individual consistency in the same behavior has a genetic basis. Behavioral consistency is also prevalent in the form of between-individual correlation of functionally different behaviors; thus, the relationship between DRD4 polymorphism and exploration may also be manifested for other behaviors. Here, in a Hungarian population of the collared flycatcher, Ficedula albicollis, we investigate how males with distinct DRD4 genotypes differ in the consistent elements of their behavioral displays during the courtship period. In completely natural conditions, we assayed novelty avoidance, aggression and risk-taking, traits that were previously shown repeatable over time and correlate with each other, suggesting that they could have a common mechanistic basis. We identified two single-nucleotide polymorphisms (SNP554 and SNP764) in the exon 3 of the DRD4 gene by sequencing a subsample, then we screened 202 individuals of both sexes for these SNPs. Focusing on the genotypic variation in courting males, we found that "AC" heterozygote individuals at the SNP764 take lower risk than the most common "AA" homozygotes (the "CC" homozygotes were not represented in our subsample of males). We also found a considerable effect size for the relationship between SNP554 polymorphism and novelty avoidance. Therefore, in addition to exploration, DRD4 polymorphisms may also be associated with the regulation of behaviors that may incur fear or stress. Moreover, polymorphisms at the two SNPs were not independent indicating a potential role for genetic constraints or another functional link, which may partially explain behavioral correlations.

Thrombosis and risk factors in female patients with a rare acquired thrombophilia: chronic myeloproliferative disorder - polycythaemia vera and essential thrombocythaemia.

OBJECTIVE: In polycythaemia vera (PV) and essential thrombocythaemia (ET), the life expectancy of the patients is greatly affected by thrombotic events. An investigation was performed of the potential association of PV/ET, and thrombotic complications with cardiovascular (CV) risk factors, a leukocyte count at the haematological diagnosis > 11.1 G/L, and the JAK2V617F mutation. PATIENTS AND METHODS: In the period 1998-2011, 128 women with a median age of 62 years were enrolled. RESULTS: The risk of thrombotic events before the diagnosis was 32.8% (42/128), while in the follow-up period it was 10.2% (13/128). The difference in the probability of thrombosis-free survival between those with at most one CV risk factor and those with two or more CV risk factors was significant (p = 0.005). The presence of two or more CV risk factors (univariate: p = 0.011; multivariate: relative risk: 4.728, 95% CI 1.312-17.040; p = 0.018) significantly increased the risk of thrombosis. Univariate analyses revealed that high blood pressure (p = 0.001), hyperlipidaemia (p = 0.005) and cigarette smoking (p = 0.051) were associated with a significantly higher risk of thrombosis. Analyses of the influence of the leukocyte count (univariate: p = 0.424; multivariate: relative risk: 1.407, 95% CI 0.359-5.507; p = 0.624) and the JAK2V617F mutation (univariate: p = 0.367; multivariate: relative risk: 1.428, 95% CI 0.316-6.460; p = 0.643) on subsequent thrombotic complications resulted in a non-signicant tendency. CONCLUSIONS: Female patients who display CV risk factors (high blood pressure, hyperlipidaemia and/or cigarette smoking) and PV or ET may well be at a higher risk of thrombotic events and require special consideration as concerns as the prevention and management of thrombotic events.

Erythropoietin receptor expression is a potential prognostic factor in human lung adenocarcinoma.

Recombinant human erythropoietins (rHuEPOs) are used to treat cancer-related anemia. Recent preclinical studies and clinical trials, however, have raised concerns about the potential tumor-promoting effects of these drugs. Because the clinical significance of erythropoietin receptor (EPOR) signaling in human non-small cell lung cancer (NSCLC) also remains controversial, our aim was to study whether EPO treatment modifies tumor growth and if EPOR expression has an impact on the clinical behavior of this malignancy. A total of 43 patients with stage III-IV adenocarcinoma (ADC) and complete clinicopathological data were included. EPOR expression in human ADC samples and cell lines was measured by quantitative real-time polymerase chain reaction. Effects of exogenous rHuEPOα were studied on human lung ADC cell lines in vitro. In vivo growth of human ADC xenografts treated with rHuEPOα with or without chemotherapy was also assessed. In vivo tumor and endothelial cell (EC) proliferation was determined by 5-bromo-2'-deoxy-uridine (BrdU) incorporation and immunofluorescent labeling. Although EPOR mRNA was expressed in all of the three investigated ADC cell lines, rHuEPOα treatment (either alone or in combination with gemcitabine) did not alter ADC cell proliferation in vitro. However, rHuEPOα significantly decreased tumor cell proliferation and growth of human H1975 lung ADC xenografts. At the same time, rHuEPOα treatment of H1975 tumors resulted in accelerated tumor endothelial cell proliferation. Moreover, in patients with advanced stage lung ADC, high intratumoral EPOR mRNA levels were associated with significantly increased overall survival. This study reveals high EPOR level as a potential novel positive prognostic marker in human lung ADC.