Molecular and flow cytometric diagnostics for evaluation of therapy efficacy in myeloid leukemias

During the past decades, a lot of progress has been made in the treatment of acute and chronic myeloid leukemia. However, despite therapy, many patients experience relapse due to the presence of remaining leukemic cells, i.e. minimal residual disease (MRD). Our study contributed to the further identification of molecular MRD targets and showed that quantitative approaches (flow cytometry and molecular techniques) can be applied in routine clinical diagnostics to evaluate therapy efficacy and to guide therapeutic interventions in myeloid leukemia

The ‘Galilean Style in Science’ and the Inconsistency of Linguistic Theorising

Chomsky’s principle of epistemological tolerance says that in theoretical linguistics contradictions between the data and the hypotheses may be temporarily tolerated in order to protect the explanatory power of the theory. The paper raises the following problem: What kinds of contradictions may be tolerated between the data and the hypotheses in theoretical linguistics? First a model of paraconsistent logic is introduced which differentiates between week and strong contradiction. As a second step, a case study is carried out which exemplifies that the principle of epistemological tolerance may be interpreted as the tolerance of week contradiction. The third step of the argumentation focuses on another case study which exemplifies that the principle of epistemological tolerance must not be interpreted as the tolerance of strong contradiction. The reason for the latter insight is the unreliability and the uncertainty of introspective data. From this finding the author draws the conclusion that it is the integration of different data types that may lead to the improvement of current theoretical linguistics and that the integration of different data types requires a novel methodology which, for the time being, is not available

The ‘Galilean Style in Science’ and the Inconsistency of Linguistic Theorising

Chomsky’s principle of epistemological tolerance says that in theoretical linguistics contradictions between the data and the hypotheses may be temporarily tolerated in order to protect the explanatory power of the theory. The paper raises the following problem: What kinds of contradictions may be tolerated between the data and the hypotheses in theoretical linguistics? First a model of paraconsistent logic is introduced which differentiates between week and strong contradiction. As a second step, a case study is carried out which exemplifies that the principle of epistemological tolerance may be interpreted as the tolerance of week contradiction. The third step of the argumentation focuses on another case study which exemplifies that the principle of epistemological tolerance must not be interpreted as the tolerance of strong contradiction. The reason for the latter insight is the unreliability and the uncertainty of introspective data. From this finding the author draws the conclusion that it is the integration of different data types that may lead to the improvement of current theoretical linguistics and that the integration of different data types requires a novel methodology which, for the time being, is not available

Stratified community responses to methane and sulfate supplies in mud volcano deposits: insights from an <i>in vitro</i> experiment

Numerous studies on marine prokaryotic communities have postulated that a process of anaerobic oxidation of methane (AOM) coupled with sulfate reduction (SR) is the main methane sink in the world's oceans. AOM has also been reported in the deep biosphere. But the responses of the primary microbial players in eliciting changes in geochemical environments, specifically in methane and sulfate supplies, have yet to be fully elucidated. Marine mud volcanoes (MVs) expel a complex fluid mixture of which methane is the primary component, forming an environment in which AOM is a common phenomenon. In this context, we attempted to identify how the prokaryotic community would respond to changes in methane and sulfate intensities, which often occur in MV environments in the form of eruptions, diffusions or seepage. We applied an integrated approach, including (i) biochemical surveys of pore water originated from MV, (ii) in vitro incubation of mud breccia, and (iii) prokaryotic community structure analysis. Two distinct AOM regions were clearly detected. One is related to the sulfate methane transition zone (SMTZ) at depth of 30-55 cm below the sea floor (bsf); the second is at 165-205 cm bsf with ten times higher rates of AOM and SR. This finding contrasts with the sulfide concentrations in pore waters and supports the suggestion that potential AOM activity below the SMTZ might be an important methane sink that is largely ignored or underestimated in oceanic methane budget calculations. Moreover, the incubation conditions below the SMTZ favor the growth of methanotrophic archaeal group ANME-2 compared to ANME-1, and promote the rapid growth and high diversity of bacterial communities. These incubation conditions also promote the increase of richness in bacterial communities. Our results provide direct evidence of the mechanisms by which deep AOM processes can affect carbon cycling in the deep biosphere and global methane biochemistry

Vegetation composition and soil microbial community structural changes along a wetland hydrological gradient

Fluctuations in wetland hydrology create an interplay between aerobic and anaerobic conditions, controlling vegetation composition and microbial community structure and activity in wetland soils. In this study, we investigated the vegetation composition and microbial community structural and functional changes along a wetland hydrological gradient. Two different vegetation communities were distinguished along the hydrological gradient; &lt;i&gt;Caricetum gracilis&lt;/i&gt; at the wet depression and &lt;i&gt;Arrhenatheretum elatioris&lt;/i&gt; at the drier upper site. Microbial community structural changes were studied by a combined in situ &lt;sup&gt;13&lt;/sup&gt;CO&lt;sub&gt;2&lt;/sub&gt; pulse labeling and phospholipid fatty acid (PLFA) based stable isotope probing approach, which identifies the microbial groups actively involved in assimilation of newly photosynthesized, root-derived C in the rhizosphere soils. Gram negative bacterial communities were relatively more abundant in the surface soils of the drier upper site than in the surface soils of the wetter lower site, while the lower site and the deeper soil layers were relatively more inhabited by gram positive bacterial communities. Despite their large abundance, the metabolically active proportion of gram positive bacterial and actinomycetes communities was much smaller at both sites, compared to that of the gram negative bacterial and fungal communities. This suggests much slower assimilation of root-derived C by gram positive and actinomycetes communities than by gram negative bacteria and fungi at both sites. Ground water depth showed a significant effect on the relative abundance of several microbial communities. Relative abundance of gram negative bacteria significantly decreased with increasing ground water depth while the relative abundance of gram positive bacteria and actinomycetes at the surface layer increased with increasing ground water depth

Carbon allocation and carbon isotope fluxes in the plant-soil-atmosphere continuum: a review

The terrestrial carbon (C) cycle has received increasing interest over the past few decades, however, there is still a lack of understanding of the fate of newly assimilated C allocated within plants and to the soil, stored within ecosystems and lost to the atmosphere. Stable carbon isotope studies can give novel insights into these issues. In this review we provide an overview of an emerging picture of plant-soil-atmosphere C fluxes, as based on C isotope studies, and identify processes determining related C isotope signatures. The first part of the review focuses on isotopic fractionation processes within plants during and after photosynthesis. The second major part elaborates on plant-internal and plant-rhizosphere C allocation patterns at different time scales (diel, seasonal, interannual), including the speed of C transfer and time lags in the coupling of assimilation and respiration, as well as the magnitude and controls of plant-soil C allocation and respiratory fluxes. Plant responses to changing environmental conditions, the functional relationship between the physiological and phenological status of plants and C transfer, and interactions between C, water and nutrient dynamics are discussed. The role of the C counterflow from the rhizosphere to the aboveground parts of the plants, e.g. via CO&lt;sub&gt;2&lt;/sub&gt; dissolved in the xylem water or as xylem-transported sugars, is highlighted. The third part is centered around belowground C turnover, focusing especially on above- and belowground litter inputs, soil organic matter formation and turnover, production and loss of dissolved organic C, soil respiration and CO&lt;sub&gt;2&lt;/sub&gt; fixation by soil microbes. Furthermore, plant controls on microbial communities and activity via exudates and litter production as well as microbial community effects on C mineralization are reviewed. A further part of the paper is dedicated to physical interactions between soil CO&lt;sub&gt;2&lt;/sub&gt; and the soil matrix, such as CO&lt;sub&gt;2&lt;/sub&gt; diffusion and dissolution processes within the soil profile. Finally, we highlight state-of-the-art stable isotope methodologies and their latest developments. From the presented evidence we conclude that there exists a tight coupling of physical, chemical and biological processes involved in C cycling and C isotope fluxes in the plant-soil-atmosphere system. Generally, research using information from C isotopes allows an integrated view of the different processes involved. However, complex interactions among the range of processes complicate or currently impede the interpretation of isotopic signals in CO&lt;sub&gt;2&lt;/sub&gt; or organic compounds at the plant and ecosystem level. This review tries to identify present knowledge gaps in correctly interpreting carbon stable isotope signals in the plant-soil-atmosphere system and how future research approaches could contribute to closing these gaps

The type N Karlhede bound is sharp

We present a family of four-dimensional Lorentzian manifolds whose invariant classification requires the seventh covariant derivative of the curvature tensor. The spacetimes in questions are null radiation, type N solutions on an anti-de Sitter background. The large order of the bound is due to the fact that these spacetimes are properly $CH_2$, i.e., curvature homogeneous of order 2 but non-homogeneous. This means that tetrad components of $R, \nabla R, \nabla^{(2)}R$ are constant, and that essential coordinates first appear as components of $\nabla^{(3)}R$. Covariant derivatives of orders 4,5,6 yield one additional invariant each, and $\nabla^{(7)}R$ is needed for invariant classification. Thus, our class proves that the bound of 7 on the order of the covariant derivative, first established by Karlhede, is sharp. Our finding corrects an outstanding assertion that invariant classification of four-dimensional Lorentzian manifolds requires at most $\nabla^{(6)}R$.Comment: 7 pages, typos corrected, added citation and acknowledgemen

Curvature homogeneous spacelike Jordan Osserman pseudo-Riemannian manifolds

Let s be at least 2. We construct Ricci flat pseudo-Riemannian manifolds of signature (2s,s) which are not locally homogeneous but whose curvature tensors never the less exhibit a number of important symmetry properties. They are curvature homogeneous; their curvature tensor is modeled on that of a local symmetric space. They are spacelike Jordan Osserman with a Jacobi operator which is nilpotent of order 3; they are not timelike Jordan Osserman. They are k-spacelike higher order Jordan Osserman for $2\le k\le s$; they are k-timelike higher order Jordan Osserman for $s+2\le k\le 2s$, and they are not k timelike higher order Jordan Osserman for $2\le s\le s+1$.Comment: Update bibliography, fix minor misprint

High CD33-antigen loads in peripheral blood limit the efficacy of gemtuzumab ozogamicin |(Mylotarg®) treatment in acute myeloid leukemia patients

Gemtuzumab ozogamicin (Mylotarg®) induces remission in approximately 30% of relapsed AML patients. We previously demonstrated that gemtuzumab infusion results in near-complete CD33 saturation in peripheral blood, and that saturating gemtuzumab levels result in continuous binding and internalization of gemtuzumab due to renewed CD33 expression. We now demonstrate that a high CD33-antigen load in peripheral blood is an independent adverse prognostic factor, likely due to peripheral consumption of gemtuzumab. Indeed, CD33 saturation in bone marrow is significantly reduced (40-90% saturation) as compared with CD33 saturation in corresponding peripheral blood samples (>90%). In vitro, such reduced CD33 saturation levels were strongly related with reduced cell kill. Apparently, high CD33-antigen loads in blood consume gemtuzumab and thereby limit its penetration into bone marrow. Consequently, CD33 saturation in bone marrow is reduced, which hampers efficient cell kill. Therefore, gemtuzumab should be administered at higher or repeated doses, or, preferably, after reduction of the leukemic cell burden by classical chemotherapy