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Flax fiber reinforced polymers (FFRP) provide a sustainable and cost-efficient alternative to synthetic fibers like carbon or glass. However, the mechanical properties of FFRP are not always sufficient for structural applications. Their strength can be enhanced by selective implementation of carbon fiber strains into the FFRP. This flax-carbon fiber hybrid material offers great potential, but is difficult to recycle, which greatly reduces the environmental benefits of FFRP.

Nickel-rich layered oxides, crucial for high-energy-density Li-ion batteries, face challenges in cycle life due to intricate chemo-mechanical degradation. This study pioneers a comprehensive approach, integrating nano X-ray computed tomography and advanced electrochemical methods, to untangle the interplay of degradation mechanisms in complex composite electrodes. The evolution of cracking in Nickel-rich cathodes is meticulously quantified under diverse operating conditions. Surprisingly, our findings unveil that, contrary to conventional wisdom, crack formation is not the primary driver of capacity decay in Nickel-rich cathodes. Instead, the limiting factor emerges from the interplay between cycling-induced cracks and a progressively growing resistivity. Cracks, amplifying electrochemically active surfaces, foster side reactions, elevating resistance, and consequently diminishing capacity and current rate capability. This novel insight redirects attention to the dynamic resistivity growth, pinpointing operating conditions as a critical contributor. This work not only advances our understanding of Nickel-rich cathode degradation but also provides a framework for strategic mitigation strategies.

In der Intensivmedizin des Erwachsenen haben in den letzten Jahren mechanische Herz-Kreislauf-Unterstützungs- (perkutane Assist Devices) und Ersatzverfahren der Herzfunktion vor allem zur Behandlung des therapierefraktären infarktbedingten kardiogenen Schocks Einzug gehalten. Dabei unterscheidet man partielle Unterstützungssysteme und die Möglichkeit eines kurzzeitigen kompletten Herz- und (Lungen)-Ersatzes mittels Extracorporeal Life Support (ECLS). Trotz Einsatz dieser Systeme bleibt der kardiogene Schock mit einer hohen Mortalität verbunden. Die Erwägung mechanischer Systeme, wie perkutaner linksventrikulärer Unterstützungssysteme und ECLS, sollte erst nach Ausschöpfung medikamentöser Therapien zur Stabilisation der hämodynamischen Zielparameter erfolgen. Die Datenlage zur Implantation perkutaner Left Ventricular Assist Devices (LVAD) oder des ECLS bei Patienten im kardiogenen Schock ist bisher noch deutlich begrenzt. Eine Empfehlung zur Implantation des ECLS gibt es in den deutschen und internationalen Leitlinien erst nach Ausschöpfung der medikamentösen Therapie im kardiogenen Schock. In anderen Fällen eines nichtinfarktbedingten kardiogenen Schocks (z. B. Intoxikation, Myokarditis) kann ein ECLS als Überbrückung genutzt werden. ECLS kann auch in Fällen der Reanimation als sogenannte E‑CPR eingesetzt werden und zeigte nach Register-Daten einen möglichen Mortalitätsbenefit bei ausgewählten Patienten. Eine weitere Sondersituation für den Einsatz von ECLS stellt die akzidentielle schwere Hypothermie mit Herzkreislaufstillstand dar, auch hier gibt es limitierte Daten für die Anwendung der Systeme. Bei fehlender Therapie-Alternative sollte aber in diesen Fällen frühzeitig über den Einsatz der Organersatzsysteme nachgedacht werden. In recent years, the widespread use of partial mechanical cardiac support and even temporary complete replacement of cardiac function has been established in many intensive care units in the treatment of refractory cardiogenic shock. There is a difference between partial left-ventricular assist devices (LVAD) and the possibility of complete heart (and lung) replacement by extra corporeal life support (ECLS). Despite the use of mechanical support devices, the mortality of cardiogenic shock remains high. The consideration of using percutaneous LVAD and ECLS in cardiogenic shock should be considered in refractory cardiogenic shock patients in addition to support by catecholamines and after early revascularization in acute coronary syndromes. However, there are no large randomized studies evaluating mechanical support systems with respect to outcome in cardiogenic shock patients. German and international guidelines do not recommend the routine use of mechanical support as a first-line treatment in cardiogenic shock patients and emphasize that their application should be restricted to patients with therapy refractory shock. In other cases of noninfarct-related cardiogenic shock (e. g., poisoning, myocarditis), ECLS use should be considered as bridging therapy. ECLS may also be considered in cardiopulmonary resuscitation which is termed E‑CPR. According to registry data, E‑CPR may reduce mortality in selected patients. A possible application of ECLS is severe accidental hypothermia with cardiac arrest despite limited data. In these rare cases, early ECLS should be considered for rewarming and stabilization.

By combining previous multilayer optics design methods a multilayer mirror (MLM) optimisation programme has been developed to provide a versatile tool for MLM design for the XUV range. The programme uses a simulated annealing algorithm to avoid the design of suboptimal multilayered stacks. Investigations have been carried out on the influence of the computational sublayer thickness used in the computation and on the algorithm for reducing the simulated annealing temperature. The optimisation programme allows variation of the angle of incident radiation, the interface roughness and the number of différent materials within the MLM structure. The possibility of optimising the performance of the MLM using différent merit functions or reflectivity profiles has been implemented. Variation of the incidence angle allows the design of polarisers by optimising at the Brewster angle and ratios of $R_s/R_p$around 103are achieved for specific wavelengths. To select a specific line from a superimposed line and continuum spectrum a selective merit function is used. By maximising the ratio of the relevant line throughput to the continuum throughput, such MLM designs can be used to select a specific line from an électron impact or laser plasma source spectrum for microscopy or microbeam radiation experiments.

Since XRM99, when the first results from the King's College laboratory scanning x-ray microscope were reported, the microscope has been redesigned to enhance its performance. The new features include scanning the laser beam, using galvanometer mirrors, to replace source scanning. The mirrors can be scanned at up to 800 Hz, with negligible noise, so that the rate-limiting factor will be the repetition rate of the laser used to form the plasma source. A mechanism to tilt the tape target surface to give a vertical x-ray beam, i.e., horizontal specimen mounting, has also been incorporated, and a comparison of source emission characteristics in the horizontal and vertical directions has been made. Previously, image quality was limited by laser and plasma generated noise, which could not be removed with direct x-ray detection. An indirect detection System is therefore undergoing tests. Finally, development of the microscope has been hampered by limited access to the lasers at the Rutherford Appleton Laboratory, and so a new laser System has been specified and ordered for installation at King's.

A numerical benchmark for 2-D variable-density flow and solute transport in a freshwater lens is presented. The benchmark is based on results of laboratory experiments conducted by Stoeckl and Houben (2012) using a sand tank on the meter scale. This benchmark describes the formation and degradation of a freshwater lens over time as it can be found under real-world islands. An error analysis gave the appropriate spatial and temporal discretization of 1 mm and 8.64 s, respectively. The calibrated parameter set was obtained using the parameter estimation tool PEST. Comparing density-coupled and density-uncoupled results showed that the freshwater-saltwater interface position is strongly dependent on density differences. A benchmark that adequately represents saltwater intrusion and that includes realistic features of coastal aquifers or freshwater lenses was lacking. This new benchmark was thus developed and is demonstrated to be suitable to test variable-density groundwater models applied to saltwater intrusion investigations. This benchmark describes the formation and degradation of a freshwater lensComparable results are salinity distributions and angles of flow vectorsSensitivity and convergence studies are included and worthiness is shown

B cells have been shown to be refractory to reprogramming and B-cell-derived induced pluripotent stem cells (iPSC) have only been generated from murine B cells engineered to carry doxycycline-inducible Oct4, Sox2, Klf4 and Myc (OSKM) cassette in every tissue and from EBV/SV40LT-immortalized lymphoblastoid cell lines. Here, we show for the first time that freshly isolated non-cultured human cord blood (CB)- and peripheral blood (PB)-derived CD19+CD20+ B cells can be reprogrammed to iPSCs carrying complete VDJH immunoglobulin (Ig) gene monoclonal rearrangements using non-integrative tetracistronic, but not monocistronic, OSKM-expressing Sendai Virus. Co-expression of C/EBPa with OSKM facilitates iPSC generation from both CB- and PB-derived B cells. We also demonstrate that myeloid cells are much easier to reprogram than B and T lymphocytes. Differentiation potential back into the cell type of their origin of B-cell-, T-cell-, myeloid- and fibroblast-iPSCs is not skewed, suggesting that their differentiation does not seem influenced by ‘epigenetic memory’. Our data reflect the actual cell-autonomous reprogramming capacity of human primary B cells because biased reprogramming was avoided by using freshly isolated primary cells, not exposed to cytokine cocktails favoring proliferation, differentiation or survival. The ability to reprogram CB/PB-derived primary human B cells offers an unprecedented opportunity for studying developmental B lymphopoiesis and modeling B-cell malignancies.

We report for the first time, to the best of our knowledge, an innovative design concept for intracavity pulse stretching in a regenerative amplifier, employing a single “grating-mirror” based on a leaky-mode grating-waveguide design. The very compact and flexible layout allows for femtosecond pulses to be in principle easily stretched up to nanosecond durations. The design has been tested in a diode-pumped Yb:CALGO regenerative amplifier followed by a standard transmission grating compressor. Sub-200-fs pulses (stretched pulses ≈110  ps) with 205-μJ energy at 20-kHz repetition rate have been demonstrated. In order to prove the robustness and potential for energy scaling of leaky-mode grating-waveguide intracavity stretcher, we generated stretched pulses with energies of up to ≈700  μJ (400-ps long) at a lower repetition rate of 10 kHz. A simple model is proposed for the study of the cavity in presence of induced spatial chirp.

We investigate the linear propagation of Gaussian-apodized solutions to the paraxial wave equation in free-space and first-order optical systems. In particular, we present complex coordinate transformations that yield a very general and efficient method to apply a Gaussian apodization (possibly with initial phase curvature) to a solution of the paraxial wave equation. Moreover, we show how this method can be extended from free space to describe propagation behavior through nonimaging first-order optical systems by combining our coordinate transform approach with ray transfer matrix methods. Our framework includes several classes of interesting beams that are important in applications as special cases. Among these are, for example, the Bessel–Gauss and the Airy–Gauss beams, which are of strong interest to researchers and practitioners in various fields.

For a reliable prediction of the NMSSM Higgs boson signatures at present and future high-energy colliders and a proper distinction of the NMSSM and MSSM Higgs sector the precise knowledge of the Higgs boson masses including higher-order corrections is indispensable. In this paper, the one-loop corrections to the neutral NMSSM Higgs boson masses and mixings are calculated in three different renormalization schemes. In addition to the DR renormalization scheme, existing in the literature, two other schemes are adopted. Furthermore, the dependence on the value of me top quark mass is investigated. From this and the variation of the renormalization scale, at one-loop level, the residual theory error due to missing higher-order corrections can be estimated to be of the order of 10%. [ABSTRACT FROM AUTHOR]

We present an Yb-CALGO thin-disk laser in continuous regime. In a slightly multimode configuration we obtain up to 29.5W of average power, corresponding to a slope efficiency of 40% and an optical-to-optical efficiency of 32%. We then design a monomode cavity, and achieve 25W of average power. The tuning range of the laser emission was from 1018 to 1052nm. In a Q-switch regime, we obtain more than 1 mJ at 100 Hz repetition rate, and 4.5W at 10 kHz repetition rate.

Hintergrund: Bei einer 39jährigen Patientin, die wegen einer akuten myeloischen Leukämie erstmalig zur Behandlung kam, fiel bei der Bestimmung der ABO-Blutgruppe eine Diskrepanz zwischen dem Nachweis der erythrozytären Merkmale (keine Reaktion mit Anti-A, Anti-B und Anti-AB) und der Serum-gegenprobe (keine Reaktion mit 0-, A1 und A2-Erythrozyten, starke Reaktion mit B-Erythrozyten) auf. Material und Methoden: Je 5 monoklonale und 5 polyklonale Anti-A-, Anti-B- und Anti-AB-Reagenzien verschiedener Hersteller wurden zur Bestimmung der ABO-Merkmale verwendet (Röhrchen-Zentrifugationsmethode, 5 min Inkubation bei Raumtemperatur). Ergebnisse: Mit keinem polyklonalen und nur 1 monoklonalen Anti-A-Reagenz, mit 3 polyklonalen und 2 monoklonalen Anti-AB-Reagenzien war das A-Antigen nachweisbar. Darüber hinaus war das H-Antigen weder mit monoklonalen noch mit Lektin-Reagenzien nachzuweisen. Anläßlich einer Folgeuntersuchung nach 7 Monaten (nach zwischenzeitlicher Chemotherapie) konnten das A- und das H-Antigen mit starken Agglutinationsreaktionen nachgewiesen werden. Schlußfolgerung: Trotz hochwertiger monoklonaler wie polyklonaler Reagenzien zur Bestimmung der erythrozytären Antigene müssen bei der Untersuchung der ABO-Blutgruppe (von Neugeborenen und Säuglingen abgesehen) die komplementären Reaktionen der Serumgegenprobe genau beachtet werden.

Abstract: Detection of lane markings based on a camera sensor can be a low-cost solution to lane departure and curve-over-speed warnings. A number of methods and implementations have been reported in the literature. However, reliable detection is still an issue because of cast shadows, worn and occluded markings, variable ambient lighting conditions, for example. We focus on increasing detection reliability in two ways. First, we employed an image feature other than the commonly used edges: ridges, which we claim addresses this problem better. Second, we adapted RANSAC, a generic robust estimation method, to fit a parametric model of a pair of lane lines to the image features, based on both ridgeness and ridge orientation. In addition, the model was fitted for the left and right lane lines simultaneously to enforce a consistent result. Four measures of interest for driver assistance applications were directly computed from the fitted parametric model at each frame: lane width, lane curvature, and vehicle yaw angle and lateral offset with regard the lane medial axis. We qualitatively assessed our method in video sequences captured on several road types and under very different lighting conditions. We also quantitatively assessed it on synthetic but realistic video sequences for which road geometry and vehicle trajectory ground truth are known.

Three new ent-trachylobane diterpenoids (1−3) were isolated and structures elucidated from Mitrephora glabra Scheff. (Annonaceae). Mitrephorone A (1) possesses a hexacyclic ring system with adjacent ketone moieties and an oxetane ring, both of which are unprecedented among trachylobanes. All compounds were evaluated for cytotoxicity against a panel of cancer cells, where 1 displayed the most potent and broadest activity, and against a battery of antimicrobial assays, where all compounds were approximately equipotent.

Bioactivity-directed fractionation of extracts of two Diospyros maritima bark samples from Indonesia, one collected at sea level in a beach forest in Java and the other collected at a slight elevation away from the sea shore on the island of Lombok, yielded a diverse set of secondary metabolites. The naphthoquinone plumbagin (1), although found in extracts of both specimens, constituted a much larger percentage of the former sample, which also yielded a series of plumbagin dimers, maritinone (2), chitranone (3), and zeylanone (4). The latter sample yielded a new naphthoquinone derivative, (4S)-shinanolone (5), and a new natural product coumarin, 7,8-dimethoxy-6-hydroxycoumarin (6), along with three other analogues of plumbagin, 2-methoxy-7-methyljuglone (7), 3-methoxy-7-methyljuglone (8), and 7-methyljuglone (9). The structures of compounds 5 and 6 were elaborated by physical, spectral, and chemical methods. All of the isolates were evaluated in both cytotoxicity and antimicrobial assays, and structure−activity relationships of these naphthoquinones are proposed. Plumbagin (1) and maritinone (2) were evaluated also for in vivo antitumor activity in the hollow fiber assay, but both were found to be inactive.

We report on ferromagnetic resonance measurements of Ga1−xMnxAs thin films with Mn contents 0.022 ≤ x ≤ 0.051. For x ≥ 0.036 and the external magnetic field normal to the thin film, we observe several resonances, which we identify as spin wave resonances. The non-quadratic mode spacing can be consistently explained by a linear gradient in the magnetic properties of the films. From the measurements, the exchange constant Acan be deduced for different Mn contents x.

MBE-grown GaN : Mn layers with Mn doping concentrations around 1020cm−3were investigated by photoconductivity measurements. From electron spin resonance (ESR), Mn is known to be mostly present in the neutral Mn3+or Mn2++ h+state, which leads to a reassignment of the known optical absorption features to charge transfer from Mn3+, either by direct photoionization at about 1.8 eV or by a photothermal ionization process via an excited state (Mn3+)*at 1.42 V higher internal energy than the Mn3+ground state. It is proposed that the Mn3+/Mn2+acceptor level is located about 1.8 eV above the valence band edge of GaN so that the nature of the acceptor wavefunction is very different from an effective-mass-like state such as the Mn2++ h+complex in GaAs : Mn. According to these experimental results, the realization of carrier-mediated ferromagnetism becomes rather unlikely in not co-doped GaN : Mn.

To study the electronic transport properties of two-dimensional electron gases confined at the interfaces of AlGaN/GaN heterostructures, Shubnikov–de Haas (SdH) and Hall measurements were performed with structures covering a wide range of sheet carrier concentrations from 2.25 × 10¹² to 1.83 × 10¹³ cm^—2. For samples with sheet carrier concentrations above 1.7 × 10¹³ cm^—2, the occupation of a second subband was observed. Fourier transformation was used to separate the contributions of both occupied subbands to the electronic transport. Quite similar quantum scattering times and effective masses of the electrons in the first and second subband were determined. In samples with lower sheet carrier concentration traces of a spin splitting could be found by investigating the angle dependence of the SdH-oscillations.

Electron spin resonance (ESR) of electrically active centers in n-type epitaxial diamond films has been measured by electrically detected magnetic resonance (EDMR). In the regime of hopping conductivity, ³¹P-related centers could be separated from a large number of P1 nitrogen centers in the substrate crystal and from carbon dangling bond defects close to the electrical contacts. One of these centers is characterized by g⊥ = 2.0026, g‖ = 2.0042, Aiso = 17.6 G, and Aaniso = 1.8 G, which is incompatible with the predictions for hydrogenic donor states of phosphorus on substitutional sites. These predictions are better fulfilled by a second spurious center with approximately g = 2.006, Aiso = 380 G, and Aaniso = 15 G.

Haemodialysis dose has been shown to have a distinct impact upon the morbidity and mortality rate in patients on regular dialysis therapy. Accordingly, the adequacy of dialysis treatment should be guaranteed.

The commitment of multipotent cells to particular developmental pathways requires specific changes in their transcription factor complement to generate the patterns of gene expression characteristic of specialized cell types. We have studied the role of the GATA cofactor Friend of GATA (FOG) in the differentiation of avian multipotent hematopoietic progenitors. We found that multipotent cells express high levels of FOG mRNA, which were rapidly down-regulated upon their C/EBPbeta-mediated commitment to the eosinophil lineage. Expression of FOG in eosinophils led to a loss of eosinophil markers and the acquisition of a multipotent phenotype, and constitutive expression of FOG in multipotent progenitors blocked activation of eosinophil-specific gene expression by C/EBPbeta. Our results show that FOG is a repressor of the eosinophil lineage, and that C/EBP-mediated down-regulation of FOG is a critical step in eosinophil lineage commitment. Furthermore, our results indicate that maintenance of a multipotent state in hematopoiesis is achieved through cooperation between FOG and GATA-1. We present a model in which C/EBPbeta induces eosinophil differentiation by the coordinate direct activation of eosinophil-specific promoters and the removal of FOG, a promoter of multipotency as well as a repressor of eosinophil gene expression.

(111) lead zirconate titanate PZT films of various thicknesses 700, 500 and 300 nm on Pt electrodes have been investigated by tapping mode atomic force microscopy (TMAFM). The PZT crystallites were found to partition into slabs of 90° domains in all cases with domain walls oriented along 〈110〉 planes. The polarization c-axis of the domains was inclined by 35° towards the surface and tilted to the surface normal alternately by +45° or —45° for a fully poled film. The grain size was found to be 200 nm, however, the domain width w scaled with the square root of the film thickness h (w = 19 nm for h = 700 nm, w = 16 nm for h = 500 nm, w = 12 nm for h = 300 nm). Furthermore, (111) PZT films (all 700 nm thickness) have been investigated on three different substrates: For (111) PZT on (111) Pt, an average domain width of 19 nm was measured (700 nm). A mean domain width of 20 nm was detected for (111) PZT on polycrystalline IrO2 and 22 nm for (111) PZT on amorphous Al2O3 (700 nm thickness). The calculated domain width is 16 nm for a film of 500 nm thickness according to the Speck-Romanov-Pompe-Streiffer theory of elastic relaxation in ferroelectric films.

CAAT/enhancer binding proteins (C/EBPs) are transcriptional activators implicated in the differentiation processes of various cell lineages. We have shown earlier that NF‐M, the chicken homolog of C/EBP beta, is specifically expressed in myelomonocytic and eosinophilic cells of the hematopoietic system. To investigate the role of NF‐M in hematopoietic cell lineage commitment, we constructed a conditional form of the protein by fusing it to the hormone binding domain of the human estrogen receptor. This construct was stably expressed in a multipotent progenitor cell line transformed by the Myb‐Ets oncoprotein. We report here that both NF‐M‐dependent promoter constructs and resident genes could be activated by addition of beta‐estradiol to the NF‐M‐estrogen receptor expressing progenitors. At the same time, we observed a down‐regulation of progenitor‐specific surface markers and the up‐regulation of differentiation markers restricted to the eosinophil and myeloid lineages. In addition to the onset of differentiation, cell death was induced with typical apoptotic features. Our results suggest that NF‐M plays an important role in commitment along the eosinophil lineage and in the induction of apoptosis.

The transforming capacity of the normal and mutant human EGF receptor (EGFR) was investigated in primary chicken cells. In fibroblasts, both N‐ and C‐terminal truncations resulted in a weak, additive oncogenic activity. However, not even double truncations caused a v‐erbB‐like phenotype. Upon EGF‐binding, on the other hand, both normal and C‐terminally truncated EGFRs resembled v‐erbB in their fibroblast transforming potential. In erythroblasts, N‐terminal truncation was sufficient to induce constitutive self‐renewal, which was enhanced by deletion of 32 C‐terminal amino acids but abolished by a larger truncation of 202 amino acids. In contrast to the normal EGFR, the receptor lacking 32 C‐terminal amino acids resembled v‐erbB in conferring erythropoietin independence for spontaneous differentiation to the transformed erythroblasts. Our results indicate that the C‐terminal domain of the EGFR is non‐essential in fibroblast transformation, but seems to be crucial for both self renewal induction and specificity of receptor function in erythroblasts.

MH2 is an avian retrovirus that contains the v‐mil and v‐myc oncogenes. In vitro it transforms chick macrophages that are capable of proliferation in the absence of growth factor. Earlier work showed that v‐myc induces macrophage transformation and that v‐mil induces the production of chicken myelomonocytic growth factor (cMGF), thus generating an autocrine system. We describe the isolation of temperature‐sensitive (ts) mutants of MH2 virus. As suggested by marker rescue experiments, one mutant bears a ts lesion in v‐mil, whereas the other carries a mutation in v‐myc. Ts v‐mil MH2‐transformed macrophages become factor‐dependent at the non‐permissive temperature (42 degrees C), while ts‐v‐myc MH2‐transformed macrophages cease growing and acquire a more normal macrophage phenotype at 42 degrees C irrespective of the presence of cMGF. Both phenotypes can be reversed by backshift to the permissive temperature. These results suggest that the gene products of v‐mil and v‐myc function independently of each other and that v‐mil is necessary for the maintenance of autocrine growth, whereas v‐myc is required to maintain the transformed phenotype.

A murine retrovirus which expresses the avain v‐myc OK10 oncogene was constructed. The virus, denoted MMCV, readily transforms fibroblasts of established lines, such as mouse NIH/3T3 and rat 208F cells, to anchorage‐independent growth in agarose. The virus also transforms primary mouse cells: (i) virus‐infected macrophages are induced to form large colonies in semi‐solid media, and can easily be expanded into mass cultures; (ii) MMCV‐infected fibroblastic cells from mouse limb buds undergo morphological transformation and grow in semi‐solid medium. MMCV thus transforms both mouse fibroblastic cells and macrophages in vitro, in a fashion similar to the v‐myc‐containing avian viruses in chicken cells. The possibility of introducing a transforming myc gene into mammalian cells by virus infection provides a novel approach for studying the mechanism of myc transformation in cells from many lineages.

We describe the purification of a novel hematopoietic growth factor from conditioned medium of a transformed macrophage cell line. The factor, termed chicken myelomonocytic growth factor (cMGF) stimulates the growth of chicken myeloblasts transformed by myb oncogene‐containing retroviruses and induces the formation of macrophage colonies in uninfected chick bone marrow cultures. The biological activity of the factor is destroyed by trypsin and by reducing reagents but not by SDS. Analysis of crude conditioned medium on non‐reducing SDS gels reveals two active species of cMGF with mol. wts. of 23 and 27 kd. Incubation of radioiodinated partially purified cMGF with myeloblasts demonstrates the specific binding of 23‐ and 27‐kd components under non‐reducing, and 25‐ and 29‐kd components under reducing conditions. Glycosylation inhibition experiments indicate that the larger molecules represent glycosylated forms of a single protein moiety. The 27‐kd species has been purified to homogeneity (80 000‐fold enrichment) and exerts its half maximal activity at 2 X 10(‐12) M and its maximal activity at 3 X 10(‐11) M. Antibodies prepared to purified cMGF completely neutralize the growth‐stimulating activity of the factor.

Our previous work showed that haematopoietic precursors transformed by the E26 avian leukemia virus undergo multilineage differentiation in response to the phorbol ester phorbol 12‐myristate 13‐acetate (PMA). Treatment of the cells with high concentrations of PMA (100 nM) favours myelomonocytic differentiation, while lower concentrations (20 nM) induce predominantly eosinophil differentiation. Here we have investigated the role of protein kinase C (PKC) in this process and found that 100 nM, but not 20 nM, PMA dramatically down‐regulates total cellular PKC activity, indicating that high PMA concentrations result in less efficient signalling than lower PMA concentrations. Consistent with these findings is the observation that very low PMA concentrations (1 nM), which presumably only moderately activate PKC, induce myeloid differentiation. This suggests the existence of two PKC thresholds which play a role in lineage commitment. To test the model, alpha‐ and epsilon‐PKC isoforms were expressed in E26‐transformed progenitors. These cells exhibited myelomonocytic differentiation even in the absence of PMA, while treatment with concentrations of PMA as high as 100 nM led to the differentiation of predominantly eosinophils and failed to downregulate the exogenous PKC. Our results suggest that different levels of PKC activity result in three different phenotypes: (i) no PKC activity maintains the progenitor phenotype; (ii) low PKC activity favours myelomonocytic differentiation; (iii) high PKC favours eosinophil differentiation.

The E26 avian leukaemia virus encodes a fusion oncoprotein consisting of truncated versions of the c‐Myb and c‐Ets‐1 transcription factors. When used to infect embryonic chicken haematopoietic cells two types of self‐renewing progenitors are obtained, namely myeloblasts and ‘MEPs’ (Myb‐Ets progenitors). In earlier work we have shown that myeloblasts transformed by the ts21 mutant of E26, which has a lesion in v‐Myb, can be induced to differentiate into macrophages following shift to the non‐permissive temperature. Here we show that the ts21 v‐Myb is temperature sensitive for DNA binding in band shift experiments and that its inactivation in transformed MEPs induces their maturation into thrombocytes. The MEP transforming capacity of v‐Myb is not confined to its fusion with v‐Ets, as it is also seen with a virus that co‐expresses tsMyb with v‐ErbB. As with wild‐type E26‐transformed MEPs, ts21‐transformed MEPs are multipotent, differentiating into eosinophils and myeloblasts following treatment with 12‐O‐tetradecanoylphorbol‐13‐acetate. In addition, ts21‐transformed myeloblasts differentiate into macrophages when shifted to the non‐permissive temperature. This shows that v‐Myb blocks haematopoietic differentiation at two distinct stages. In contrast, v‐Ets inactivation in MEPs transformed by a ts E26 mutant with a lesion in the corresponding oncoprotein leads to their differentiation into erythrocytes, myeloblasts and probably eosinophils. These data show that the two domains of Myb‐Ets selectively affect decision making processes in different types and stages of haematopoietic cells.

A non‐leukemogenic version of the v‐myb oncogene causes in vitro transformation of avian myeloblasts, which are dependent on chicken myelomonocytic growth factor (cMGF). We have shown that this version of v‐myb, when combined with the erythroleukemia‐inducing v‐erbB oncogene, is capable of causing a mixed myeloid and erythroid leukemia. Myeloid leukemic cells transformed by this construct produce cMGF. To test whether autocrine growth stimulation via cMGF is the essential contribution of the tyrosine kinase oncogene v‐erbB in avian myeloid leukemogenesis we constructed another retrovirus containing both the non‐leukemogenic v‐myb and the cMGF cDNA. This virus induced myeloid leukemia at high efficiency. In a third construct we combined v‐myb with the human EGF‐receptor gene. Myeloid cells transformed by this construct could be stimulated to grow by the addition of cMGF or EGF. Growth stimulation with EGF was blocked by a cMGF antiserum indicating that activation of a normal tyrosine kinase‐type receptor induces cMGF expression but does not bypass the cMGF requirement. We conclude that cMGF plays a key role in the growth regulation of normal and transformed avian myeloid cells.