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In the last years a lot of international effort has been invested in high temperature resistant ceramic structures. Especially the outer thermal protection system (TPS) of the X-38 re-entry vehicle was regarded for all participants as a great challenge to both the technological progress and international cooperation of the involved companies respectively. Several German companies, MAN-T, Astrium and DLR, were directly involved in the responsibility of sufficient TPS structures of the vehicle in particular for the nose cap and within the body flap development. During the development work of the fully ceramic body flaps (two symmetrical body flaps are located in parallel at the lower rear position of the X-38 vehicle, figure 1;2), which was carried out by MAN-T in Augsburg, two mentionable qualification test campaigns were necessary and conducted at DLR Stuttgart focussed on two important bearing parts of the flap system (Fig. 2), the so called EMA = electromechanical actuator -bearing and the hinge bearing attachment system. Under contract of MAN-T and coordinated by ESA (European Space Agency) DLR Stuttgart tested the EMA bearing first in the summer of 2000 and one year later the hinge bearing attachment system. Both components have completely been made of C/SiC materials and developed, manufactured and delivered by MAN-T. Within the two exciting and also perception rich test campaigns the re-entry conditions were simulated thermally, mechanically and in an oxidizing atmosphere according to the X-38 re-entry trajectory close to reality as possible.

Since the component mass in space applications is very critical and new developments from CMC materials are on the rise with a high degree of complexity, the exact, detailed analysis of these components is becoming increasingly important to make full use of the material properties. However, material properties of CMC, especially in transverse direction, are often poorly documented, thus leading to compromises with regard to analysis reliability, especially in the use of failure criteria. Due to very limited experience in determination of failure criteria for ceramic matrix composites, it seems necessary to develop a test device to determine those values for material quality assurance and for the verification of analytical prediction tools. To provide a reliable statement about the failure criteria it is necessary to define stress conditions close to the material’s limit. Starting from the one-dimensional stress condition the two-dimensional state is attained by applying a defined shear stress. On the basis of these data a model for the failure of the structure can be derived, which can be part of future design tools of ceramic constructions. At the beginning of the project finite element simulations were performed to optain a suitable sample geometry which provides a reliable prediction of the stress distribution. To reach the favorite stress-case at testing conditions the sample was exposed to combined tension and torsion. It was possible to apply both loads, tension and torsion separately from each other by a special mechanic integrated into the hot test facility. To avoid interactions due to tolerances of manufacturing and the stiffness of the facility, special constructive measures were necessary. The construction of the test facility is suitable for C/C-SIC samples at room temperature conditions and high temperature conditions (up to 1700 K), respectively. The aim of this work was to have on the one side a prediction tool as simple as possible and on the other side to have a simple test opportunity for the verification. This contribution presents an overview of the investigations within the project so far.

A 3-year-old female rabbit ( Oryctolagus cuniculi) presented with apathy and indisposition for 2–3 days. Palpation revealed a mass in the caudal abdomen, namely, in the wall of the uterus. Ovariohysterectomy was performed, and the tissues were submitted for histopathologic examination. The mass consisted of 3 different (trophoblastic, syncytiotrophoblastic, and cytotrophoblastic) neoplastic cell types originating from the uterus. Immunohistochemistry was positive for cytokeratin in all 3 neoplastic cell types, and the syncytiotrophoblasts were positive also for human chorionic gonadotropin. Together these features allow the diagnosis choriocarcinoma. This report documents the first case of a spontaneous choriocarcinoma in a rabbit.

Procedural abstraction (PA) extracts duplicate code segments into a newly created method and hence reduces code size. For embedded micro computers the amount of memory is still limited so code reduction is an important issue. This paper presents a novel approach to PA, that is especially targeted towards embedded systems. Earlier approaches of PA are blind with respect to code reordering, i.e., two code segments with the same semantic effect but with different instruction orders were not detected as candidates for PA. Instead of instruction sequences, in our approach the data flow graphs of basic blocks are considered. Compared to known PA techniques more than twice the number of instructions can be saved on a set of binaries, by detecting frequently appearing graph fragments with a graph mining tool based on the well known gSpan algorithm. The detection and extraction of graph fragments is not as straight forward as extracting sequential code fragments. NP-complete graph operations and special rules to decide which parts can be abstracted are needed. However, this effort pays off as smaller sizes significantly reduce costs on mass-produced embedded systems.

The aim of the study is to evaluate the test-retest reliability of measures of isokinetic and isometric leg strength and joint function among individuals exhibiting symptoms of mild osteoarthritis. Reliable procedures are needed to assess the effectiveness of an intervention on osteoarthritic symptoms.Test-retest reliability of two leg strength protocols was assessed using the intraclass correlation coefficient (R). Testing was completed on two occasions separated by 7 days. Eighteen subjects (9 male and 9 female; 54.1+/-11 years) completed an isokinetic testing trial, which consisted of a set of 5 maximal repetitions of the quadriceps and hamstrings at 60 deg/s followed by a set of 15 maximal contractions at 180 deg/s with a 2-min rest between sets and an isometric testing trial, which consist of 3 maximal contractions of the quadriceps for 6 s with a 30-s rest between contractions at 30, 45, and 80 degrees of knee flexion for a total of 9 isometric contractions. A 90-s rest occurred between angles.Most of the isokinetic variables showed moderate to high intraclass reliability (ICC). Two of the calculated isokinetic variables (work fatigue at 180 degrees /s for extension and for flexion) showed low intraclass reliability (ICC=0.78, resp. ICC=0.6). All calculated ICC values of the isometric variables were moderate to high.Test-retest reliability of isokinetic and isometric leg strength was high, allowing the intervention protocol to monitor changes in leg strength and joint function among those exhibiting symptoms of mild osteoarthritis.

A 24-year old male sulfur-crested Cockatoo (Cacatua galerita) was presented with a subacute perforation of the cornea without involvement of the lens. The bird was treated conservatively and the eye remained quiescent up to a second traumatic corneal perforation associated with a lens capsule rupture 15 months later. Due to the second perforating trauma of an already blind eye involving the lens, evisceration of the eye was performed. Two months after surgery the cosmetic result was excellent. Treatment options for perforating ocular traumas in captive birds are discussed in detail.

Two groups of 22 budgerigars (Melopsittacus undulatus) were housed for 12 months under identical conditions. One group was fed a commercial seed mixture plus carrots and a mineral supplement, and the other group was fed a commercially formulated diet plus carrots. Samples of blood and faeces were collected initially and after three, six, nine and 12 months. There were no significant differences between the haematological values of the two groups. The group fed the seed mixture had significantly higher concentrations of glucose, albumin, triglycerides and uric acid, and higher activity of aspartate aminotransferase, but the values were within the published reference ranges for normal birds. There were no significant differences between the faecal samples from the two groups, except that the fungus Macrorhabdus ornithogaster was identified in 48.3 per cent of the samples from the group fed the commercially formulated diet but from only 3.4 per cent of the samples from the group fed the seed mixture.

Crop disorders are very common in small psittacine birds. Psittacine birds are very curious and like chewing on different materials. Therefore, they are predisposed to ingest foreign material. In the literature only very few cases have been reported. This case report describes the clinical examination, the diagnostic workup and the ingluviotomy in a cockatiel with a bezoar in the crop.

The transport of baggage through airports by means of individual vehicles imposes severe challenges on a central control system. In this paper, a decentralised control concept is described, which can overcome the deficiencies of central control systems. The decentralised concept consists of (a) a market-based strategy for the assignment of transportation tasks to vehicles and (b) a vehicle routing mechanism in analogy to internet data routing mechanisms. Extensive simulation tests show that significant advantages can be achieved regarding travel time. The concept can be transferred to other kinds of transportation systems, such as autonomous guided vehicles in factories and ports, and furthermore to other allocation problems for mobile resources.

New propulsion systems play a key role for future space transportation systems (STS). While high efficiency with respect to specific impulse is mandatory aspects concerning system design (complexity, manufacturing, weight), operating aspects (reusability, maintenance, high reliability and safety) and cost reduction attract increasing attention. A significant step forward seems to be the application of high temperature usable ceramic matrix composites (CMC) within a cryogenic combustion chamber design. The approach is using a porous fibre ceramic inner combustion chamber liner. Operating temperatures of the CMC material lie far upper than 1800 ◦C. Nevertheless an appropriate cooling method has to be applied accompanied by temperatures of about 2700 ◦C running the combustion process. While the porous CMC is responsible for both thermal load absorption and the effusion cooling the mechanical load carrying structure consists on a carbon fibre reinforced plastic (CFRP) outer shell. Using both ring shaped ceramic combustion chamber segments on 1-10 MPa pressure levels and a complete ceramic thrust chamber design on 1 MPa pressure level samples demonstrated already the physical principles. The paper will give an overview of the current development status, whereby the experience achieved so far is very promising out looking to the general goals.

Micropump additive systems allow for continuous modification of cardioplegia composition during heart surgery. Although the use of such systems in warm heart surgery is theoretically desirable, the role of the systems has been clinically limited by coronary vasoreactivity with higher potassium concentration and unreliable mechanical arrest at lower potassium concentration. Adenosine, a potent coronary vasodilator and arresting agent, has the potential to reduce the potassium concentration required for arrest and to improve distribution of cardioplegia. However, clinical use of adenosine has been limited by a short half-life in blood and difficulty in titrating the dose. This study tested the hypothesis that continuous addition of adenosine with an in-line linear micropump system would facilitate whole blood hyperkalemic perfusion for cardiac surgery.Canine hearts (n = 9) were randomized to 20 minutes of arrest with whole blood cardioplegia or cardioplegia with adenosine at either low (0.5 M) or high (8 M) concentration. Potassium was supplemented at an arresting dose (24 mEq/L) for 5 minutes and then at a maintenance dose (6 mEq/L) for an additional 15 minutes. Coronary flow was held constant (4 mL/kg per minute), and aortic root pressure was measured. Myocardial performance was assessed by measurement of the end-diastolic pressure to stroke volume relationship at constant afterload. Myocardial tissue perfusion was evaluated with colored microspheres.During the initial period of high-concentration potassium arrest, coronary resistance rose progressively regardless of adenosine addition. Coronary resistance remained elevated during the period of low potassium perfusion, except when high-concentration adenosine was added. With addition of 8 M adenosine, coronary resistance returned to baseline, and left ventricular endocardial perfusion was augmented. Electromechanical quiescence improved with adenosine perfusion and was complete with high-dose adenosine addition. Function was preserved in all hearts.Use of a modern micropump system allowed for continuous addition of adenosine and potassium to whole blood cardioplegia. Adenosine minimized potassium-induced coronary vasoconstriction and improved endocardial perfusion and mechanical quiescence. These findings supported addition of adenosine to the perfusate during warm whole blood cardioplegia.

The protozoan parasite Neospora caninum is one of the most important infectious abortion causes in cattle worldwide. In a Swiss case-control-study we investigated 113 abortion problem farms and 113 control farms. It was possible to detect N. caninum in 21% of 242 investigated aborted fetuses by PCR upon brain samples. Eighty-four % of mothers aborting N. caninum positive fetuses were serologically positive for this parasite. The seroprevalence for N. caninum of all aborting mothers was 44%. Within a period of 3 to 12 months 4,505 cattle from the participating farms were investigated serologically at two different time points. Strong fluctuations of the specific antibody concentration could be observed, resulting in a conversion to seronegativity in the second blood sample in 39% of formerly seropositive animals. Eighteen months after the end of the study, 42 case- and 42 controlfarms were questioned about their present abortion-status. Analysis of the questionnaire revealed that 80% of the former abortion problem farms observed an improvement of the situation. However, in 43% of those farms no preventive measures had been taken and no significant differences in hygiene, forage and animal turnover could be observed between case- and control-farms. Additionally, no significant differences were detected concerning risk factors such as the presence of farm dogs and the disposal procedure for placental and fetal material.

This paper presents an alternative to distance-based neural networks. A distance measure is the underlying property on which many neural models rely, for example self-organizing maps or neural gas. However, a distance measure implies some requirements on the data which are not always easy to satisfy in practice. This paper shows that a weaker measure, the similarity measure, is sufficient in many cases. As an example, similarity-based networks for strings are presented. Although a metric can also be defined on strings, similarity is the established measure in string-intensive research, like computational molecular biology. Similarity-based neural networks process data based on the same criteria as other tools for analyzing DNA or amino-acid sequences.

The question addressed in this paper is which types of spatial reference human users employ in their interaction with a robot and how a cognitively adequate model of these strategies can be implemented. Experiments in human-robot interaction were carried out which show how human users approach an artificial communication partner which was designed on the basis of empirical findings regarding spatial references among humans. The results are considerable differences in the strategies which speakers employ to achieve spatial reference in human-robot interaction and in natural communication.

It is still under discussion whether antibiotics are effective in the treatment of acute sinusitis. Moreover, they are known to have considerable side-effects. In contrast, complementary approaches are reported to have little side-effects and an equivalent efficiency.To assess the success of conventional and complementary treatments of acute sinusitis and to estimate the patient numbers needed to confirm therapeutic equivalence. Treatment success was measured by three different scores, assessed by both patients and physicians.Multicentre (2 complementary and 3 conventional ENT centres), non-randomised, controlled clinical trial with 63 patients (complementary group 30, conventional group 33 patients). To control for confounders treatment differences were estimated by propensity score techniques.The choice of medication was entirely left to the physician. We recommended to use antibiotics, secretolytics and symptomimetics in the conventional group and a combination of the herbal remedy Sinupret((R)) and the homeopathic remedy Cinnabaris 3X in the complementary group.Treatment differences varied substantially depending on the outcome measure, but they were always not clinically relevant. Conventional treatment was slightly better when the outcome was assessed by the physicians (1.8 score points) but slightly worse when it was assessed by patients (0.2 score points) or in terms of the HCG-5 quality of life score (0.8 score points). p values were always0.3.Both treatments appear to be equally effective (or ineffective). Results might be biased because both treatment groups differed substantially. Randomised trials including at least 400 patients are needed to produce valid results.

In the title coordination polymer, {[Co(C(3)H(7)COO)(2)(H(2)O)]·0.7H(2)O}(n), the Co(2+) cation is coordinated by four bridging butano-ate anions and two bridging water mol-ecules in a severely distorted octa-hedral geometry. The Co(2+) cations are linked by means of bridging ligands into polymeric chains along [010]. These chains are further connected to each other through hydrogen bonds involving partially occupied disordered water mol-ecules; thus, sheets parallel to (001) are formed. One of the positions of disordered water O atom lies on a twofold axis. Two atoms of the aliphatic chain of one of the butanoate anions are disordered over two positions each.

Antibiotic resistance of Staphylococcus aureus has been surveyed by eight city laboratories of the Aquitaine area, during a six month-period (january to june 1998). Antibiotic susceptibility testing has been performed by the disk diffusion method, and the results have been collected and analysed using the SIRscan system. After elimination of the redundant strains, a total of 747 isolates has been retained. They were mainly isolated from pus (64%) collected from patients of the community (40%) or hospitalized in 30 private clinics or nursing homes. The percentages of resistant strains (community/institutions) were: benzylpenicillin: 90% (87/92%), oxacillin: 39% (23/50%), kanamycin: 37% (22/47%); gentamicin: 13% (8/16%), tobramycin: 37% (21/47%), amikacin: 21% (13/27%); netilmicin: 6% (5/7%), erythromycin: 33% (30/35%), spiramycin: 72% (77/69%), lincomycin: 24% (17/29%), pristinamycin: 2% (1/2%), tetracycline: 17% (14/19%); pefloxacin: 40% (25/50%), fosfomycin: 9% (6/12%), rifampicin: 10% (7/13%), fusidic acid: 14% (11/15%), cotrimoxazole and vancomycin: 0%. Meticillin-susceptible strains of S. aureus were mostly sensitive to other antibiotics (or = 6% resistant strains, except for erythromycin: 22%). Among meticillin-resistant S. aureus, heterogeneous strains with a KT phenotype, and various resistance patterns to the remaining antibiotics were predominant (61%), compared to the homogeneous strains with a KTG phenotype and multiresistant to the other antibiotics (32%). The frequencies of resistant strains were highly variable depending on the specimen, the laboratory and the health care institution, except for cotrimoxazole and vancomycin which were always active.

Although radiotherapy is widely used as additional treatment following chemotherapy, its precise role has never been clearly proven. Relapses tend to occur in previously involved bulky sites. Non-randomized studies may suggest a positive effect of the addition of radiotherapy. This effect however, might also be caused by selection. Randomized studies have not resulted in a survival advantage for the patients treated with additional radiotherapy compared to no further treatment or additional chemotherapy. The SWOG study 7808 suggest a 20% benefit in remission duration for the nodular sclerosis histology subgroup. Definitive conclusions have to wait for more mature results of randomized studies including the ongoing EORTC study and the possibility to perform an overview of all studies.

The potential of mature central nervous system (CNS) neurons to regenerate after injury represents a fundamental issue in neurobiology. The regional expression of proteins associated with axonal elongation, such as microtubule-associated protein 1B (MAP1B), its phosphorylated isoform (MAP1B-P), growth-associated protein 43 (GAP-43), and polysialylated neural cell-adhesion molecule (PSA-NCAM), was examined using immunohistochemistry from 24 hours to 2 months following lateral fluid percussion brain injury of moderate severity (2.4-2.6 atmospheres) in anesthetized rats. Uninjured (control) rats were subjected to anesthesia and surgery without injury or were subjected to anesthesia alone. Within the site of maximal injury, only increases in MAP1B and MAP1B-P were observed. Increased immunoreactivity was observed bilaterally for all growth-related proteins that were evaluated. By 24 hours postinjury, MAP1B and MAP1B-P increased within the cortex (P0.01) and the hippocampus (P0.001), whereas MAP1B-P also was elevated in the thalamus (P0.05). Within the dentate gyrus, increased immunoreactivity was observed for all proteins examined. By 48 hours postinjury, GAP-43 was elevated bilaterally within the inner molecular layers of the dentate gyrus (P0.005) and within the stratum lacunosum moleculare (P0.01), the stratum radiatum (P0. 005), and the stratum oriens (P0.05) of the hippocampus. Increased numbers of PSA-NCAM-labeled neurons were observed in the granule cell layers of the dentate gyrus from 48 hours through 2 weeks postinjury (P0.0005). The bilateral nature of increased expression of growth-related proteins differs from unilateral patterns of neuronal degeneration previously characterized for the lateral fluid-percussion model of brain injury. Taken together, these results suggest the existence of a temporary posttraumatic state in which the CNS may have increased regenerative potential. Enhancement of such a response may be one therapeutic strategy in treating CNS injury.

MAP1B is a microtubule-associated phosphoprotein that is particularly highly expressed in developing neurons. There is experimental evidence that it plays an important role in neuronal differentiation, especially the extension of axons and dendrites, but exactly what role is unclear. Recent experiments have shed light on the gene structure of MAP1B and identified some of the kinases that phosphorylate the protein. Implicit in these findings is the idea that MAP1B regulates the organisation of microtubules in neurites and is itself regulated in a complex way and at a number of levels.

The low abundance of soluble neurofilament (NF) subunits in mature axons has suggested that newly synthesized NF proteins rapidly assemble into highly stable polymers and associate with the Triton X-100-insoluble cytoskeleton. Here we present evidence for multiple populations of NFs and NF subunits, distinguished by differential solubility in Triton, within perikarya and axons of neurons in situ and in culture. We further demonstrate, using microinjection of "tagged" NF subunits and by pulse-chase radiolabeling of endogenous NF subunits, that these soluble NF populations represent precursors for incorporation into the axonal cytoskeleton.

Testing the ability of commercial compounds to provide an effective disinfection of instruments requires test conditions that are close to reality which includes the proper selection of the material used to contaminate the test objects. The adhesion of the material must be strong enough to keep it attached to the test object during and after insertion into the disinfectant solution. Its characteristics should come as close as possible to those of the contaminations encountered in practice. The guideline for instrument disinfectants published by the Robert Koch-Institute recommends the use of coagulated blood. Accordingly, heparinized sheep blood is mixed with the test germs, and protamin is added to initiate coagulation. In the present investigation we compared this contamination procedure with a second one, in which coagulation was achieved by adding a CaCl2 solution to citrate blood. We also included agarose as an almost inert contaminant in our experiments. The results showed that protamine is able to increase the microbicidal efficacy of formaldehyde on staphylococci significantly. When these test germs were embedded either in citrat blood or in agarose, it took about twice the disinfectant concentrations to achieve the same microbicidal effects as with protamine blood (Fig. 1). Remarkably, the results obtained with citrate blood were the same as those with agarose, regardless of the differences in material between the two contaminants. It should also be noted that the microbicidal effect of the formaldehyde proved to be almost independent from the amount of contaminant per test area, hence, from the thickness of the layer. When M. terrae was employed as test germ, the results obtained with protamine blood and citrate blood, respectively, as contaminants were identical (Fig. 2). The same was true for the other test germs investigated, except for E. faecium (Fig. 3). The addition of even very small amounts of protamine to the embedding compound, agarose led to a substantially increased efficacy of the formaldehyde against staphylococci (Fig. 4). This effect was especially distinct in suspension (Fig. 5). Whenever the efficacy of formaldehyde-containing disinfectants is to be tested and evaluated, one should be aware of this synergism between protamine and formaldehyde. In these cases, it is advised to employ other contaminating agents, such as coagulated blood prepared by addition of CaCl2 to citrate blood.

This report describes the presence of a group of tau-like proteins (TLPs) in goldfish central nervous system. The TLPs were immunoreactive with antibodies that recognized the carboxy-terminal domain of mammalian tau, but not with antibodies that recognized the amino-terminus. The TLPs of goldfish exhibited the basic properties of tau proteins including neuronal specificity, structural heterogeneity, heat stability and the ability to co-assemble with tubulin. We propose that TLPs may represent a precursor of tau, that share the microtubule binding domain and the carboxy-terminal domain with mammalian tau proteins. In contrast the amino-terminus of the TLPs is much shorter and may represent a more variable domain of tau proteins.

MAP1B is a major cytoskeletal protein in growing axons and is strongly regulated during brain development. The present studies compare the expression of MAP1B mRNA, the protein, and its phosphorylated isoform in spinal cord and dorsal root ganglia (DRGs) with brain. In spinal cord and brain, MAP1B mRNA levels were highest in early stages of development, decreased several fold during postnatal development, and remained low in adults. In contrast, there were no significant changes of MAP1B mRNA levels during development of DRG and they remained high in adults. The levels of MAP1B protein decreased in brain and spinal cord in parallel with the changes of their mRNA. The protein levels in DRG remained relatively high but declined in the sciatic nerve. Phosphorylated MAP1B was expressed in high levels during the early stages of development in brain, spinal cord, and sciatic nerve and decreased rapidly to undetectable levels postnatally except for sciatic nerve where it remained detectable. Immunohistochemical analysis showed that phosphorylated MAP1B was absent from DRG cell bodies at all stages but was present in axons of DRG and motor neurons in both spinal cord and sciatic nerve. Immunostaining also confirmed Western blot analysis indicating that MAP1B was initially abundant within the spinal cord but was at later stages present only in motor neurons and the central processes of DRG neurons. These results reflect differential distribution of MAP1B isoforms at different stages of development and in different regions of the nervous system.

The low abundance of soluble neurofilament (NF) subunits in mature axons has suggested that newly synthesized NF proteins rapidly assemble into highly stable polymers and associate with the Triton X-100-insoluble cytoskeleton. The dynamic nature of these subunit associations in vivo remains unresolved, and the applicability of this assembly model to NFs in other neuronal compartments or to developing neurons is unknown. Here, we report that a unique pool of Triton X-100-soluble, extensively phosphorylated, high molecular weight NF subunits (NF-H, or H-200) are abundantly expressed in the mouse CNS during early postnatal development and persist in the perikaryal compartment of some mature neurons. Triton-soluble H-200 subunits appeared at postnatal day 14 (P14) and remained high through P60, beyond which the percentage declined to marginal levels by P120. Medium and low molecular weight NF (NF-M and NF-L, respectively) were at all times only detectable within the cytoskeleton. Comparison of soluble and cytoskeleton-associated H-200 immunoreactivity indicated that certain phosphorylation-dependent epitopes were confined to the cytoskeleton. Pulse-chase radiolabeling analyses in optic pathway demonstrated that some Triton-soluble NF-H subunits are extensively phosphorylated within retinal perikarya before they are incorporated into Triton-insoluble structures. These findings indicate that the assembly behaviors of NF-H differ substantially from those of NF-M and NF-L, and that the interaction of NF-H with NFs may be more dynamic than is generally recognized, especially during brain development and within specific compartments of mature neurons.

The use of leukocyte-depleted blood components has become the standard therapy for multiply transfused patients during the past few years, as a measure to reduce the frequency of alloimmunization and refractoriness. We assessed frequency and causes of refractoriness, defined as a repeated 24-h post-transfusion platelet count below 20,000/microliters, in 145 consecutive patients who received three or more single-donor platelet concentrates during a 1-year period. Flow-cytometric detection of anti-platelet antibodies and a glycoprotein-specific ELISA were applied for the diagnosis of alloimmunization. Forty patients (27.6%) had at least one episode of refractoriness. In 25 of these 40 patients (62.5%), nonimmune factors (fever, sepsis, coagulopathy, splenomegaly) alone were the cause. In 15 refractory patients alloantibodies were detected. In seven patients (17.5%), alloimmunization alone caused an inadequate transfusion response, while in eight refractory patients (20.0%) alloimmunization and fever or sepsis were present. HLA antibodies were detected in 17 patients (11.7%); three patients (2%) had platelet-specific antibodies in addition to HLA antibodies; in two patients panreactive platelet antibodies were detectable. All 17 patients had a history of previous transfusions or pregnancy. We did not observe primary immunization in patients transfused exclusively with filtered (leukodepleted) blood products. Our data suggest that alloimmunization in patients with a negative risk history can be prevented by the exclusive use of leukodepleted blood components.

The results of the present experiments demonstrate that fetal spinal cord transplants placed into the site of a complete transection in newborn rats permit the development of complex patterns of locomotion. These patterns differ in some respects from normal, but include weight support, appropriate postural adjustment, and coordination between forelimbs and hindlimbs. 5-HT agonists administered to transplanted rats can further modify these motor patterns in ways that may prove able to enhance locomotion. When placed into lesion cavities in adult spinal cord, cells genetically modified to express neurotrophins can survive, differentiate, and mimic at least one consequence of fetal transplants, rescue of axotomized neurons from retrograde cell death.

In this study we analyse structural changes of the neurotransmitter acetylcholine (ACh) under the influence of phenol and the electrolytes Li+, Na+, K+, Cl-, Br- and I-. By FT-IR difference spectroscopy, spectral changes, especially in the region of the v C-N-C/C-O-C around 1250-1240 cm-1, are investigated. Our data show a shift of the band envelope in this region to lower wavenumber in the presence of phenol and I- and to higher wavenumber in the presence of the cations. From studies with ethyl acetate we find shifts of the v C-O-C to lower wavenumber under the influence of Li+ ions. We also find major changes of the band envelope in the presence of phenol. No such changes are found if AChCl is compared to AChI.

The differentiation of hematopoietic stem cells to mature cells is essential for the function of the hematopoietic system. Disturbance of this process can lead to the emergence of Acute Myeloid Leukemia (AML). AML is characterized by an accumulation of immature, malignant blasts, which disturb the function of the “normal” hematopoietic cells. The differentiation to myeloid cells is regulated among others by transcription factors. Growth factor independence 1 (GFI1) is such a hematopoietic transcription factor regulating the differentiation of myeloid cells. We sought to investigate whether different Gfi1 levels are causative for emergence of AML and how different levels of Gfi1 might influence the prognosis of patients. Using published expression array data, we observed that Gfi1 is expressed at a lower expression level in blast cells and in leukemic stem cells compared to the control non-malignant cells and stem cells. We then correlated Gfi1 expression level in blast cells of patients from different centers in with the event free survival. In Essen and Dresden (Germany), low expression levels in blast cells were (n=39) associated with an inferior prognosis (EFS 9 months for low expression compared to 42 months; p=0.0095). We confirmed our observation with an independent cohort from Rotterdam and Nijmegen. Patients with low Gfi1 expression (n=32) had an inferior event free survival (9 months) compared to patients with higher Gfi1 levels (n=144; 17 months; p=0.02). To further investigate how different levels of Gfi1 might influence initiation and progression of leukemia, we used mice expressing Gfi1 at different levels, i.e. Gfi1 deficient mice (Gfi1KO), mice heterozygous for Gfi1 (Gfi1 het) or mice expressing Gfi1 only at 20% of normal Gfi1 expression levels (Gfi1KD). We used different murine AML models to examine the role of Gfi1 in AML development. First we crossed these mice with Nup98HoxD13 mice that recapitulate MDS disease course. We observed that knockdown of Gfi1 (Gfi1KD n=15, P=0.05) and heterozygosity of Gfi1 (Gfi1 het) (n=12) accelerated AML development and were associated with higher blast cell number compared to Gfi1 wt mice (n=16). Interestingly, complete loss of Gfi1 (Gfi1KO, n=16) inhibited leukemia development. To confirm our findings, we used an independent approach. It has been shown previously that enforced retroviral expression of certain onco-fusion proteins such as MLL-AF9 or AML1-ETO9a or proteins such as MN1 can cause AML in mice. To this end we transduced lineage negative (Lin-) cells from the different mouse strains with retroviruses overexpressing these different proteins and plated the Lin-cells in methycellulose media. Similar to above, transduced Gfi1 KD cells generated more colonies and proliferated at higher levels than wt or Gfi1 KO cells (ranging between 1,5 to 4 fold KD compared to wt, depending on oncofusionprotein or oncogene, p=0.05). We also transplanted these cells into lethally irradiated mice. Again, mice transplanted with MLL-AF9 transduced Gfi1 KD cells (n=6) developed leukemia faster than mice transplanted with transduced wt (n=8; p= 0.05). We hypothesized that if lower expression of Gfi1 promotes leukemia formation, then overexpression of Gfi1 should inhibit leukemia formation. To this end we transduced Lin neg cells simultaneously with retroviruses overexpressing either MLL-AF9 or AMLETO9a and either Gfi1 or an empty vector. The cells were then plated in methycellulose and cells overexpressing Gfi1 generated fewer colonies (between 3-5 fold less, depending on oncogene, p=0.01) than cells transduced with an empty control vector. Thus, up to now our data suggests that decreased levels of Gfi1 influence prognosis of AML development and are involved in the pathogenesis of AML. On a molecular level, we found that knock-down and complete loss of Gfi1 leads to deregulation of genes in AML development such as HoxA9. However, whereas Gfi1KD cells show a normal response to apoptotic events, complete loss of Gfi1 is associated with a very high level of spontaneous apoptosis, possibly explaining why knock-down but not complete loss of Gfi1 accelerates AML development. In summary we demonstrate that Gfi1 plays a crucial role in AML development depending on the expression level, which in turn might explain the role of Gfi1 in human AML. Disclosures: No relevant conflicts of interest to declare.

Background Patients with rheumatoid arthritis (RA) share an increased risk of diastolic heart failure with normal ejection fraction (HFNEF), which is often underrecognized. Age, female gender and history of hypertension are important risk factors. Also, persistant disease activity and disease duration have been shown to be significant contributors. Therefore, effective screening for heart failure should be part of follow-up evaluation in RA-patients. However, not all patients with HFNEF are symptomatic. In contrast, RA-related fatigue and functional impairment may influence symptoms of heart failure and interfere with exercise testing. Objectives To determine diagnostic value of symptoms, laboratory results, and technical findings for classification of HFNEF in RA-patients. Methods We analyzed data of our prospective heart failure study of consecutively recruited RA-patients showing up in our community based outpatient-clinic. All patients were interviewed using a standardized questionnaire. Clinical signs were evaluated based upon Framingham criteria. Laboratory tests included NT-proBNP. Echocardiography contained tissue doppler and global longitudinal strain (GLS) imaging. Results 162 pat., n=110 (68%) female, mean (SD) age 61.3 (±13.1) years, mean disease duration 12.5 (±11.4) years, mean DAS28 2.8 (±1.0) were enrolled. Appropriate echocardiographic data was available in 155 pat. LVEF 1 and were classified having systolic heart failure. Of the remaining 149 pat. with normal EF, 62 (41,6%) had symptoms of NYHA-class>1, and HFNEF according to ESC criteria was finally classified in 31 (21%) pat. In the group with normal EF, hypertension was found in 83 (56%), diabetes in 21 (14%), GFR Conclusions When screening RA-patients, peripheral edema, dyspnea on exertion, nocturia, increased NTproBNP, high grade diastolic dysfunction, and abnormal GLS are main indicators of HFNEF. There is low diagnostic value of other symptoms and clinical findings. Disclosure of Interest None Declared

Background Increased prevalence of chronic heart failure is observed in patients with rheumatoid arthritis (RA) and heart failure with normal ejection fraction (HFNEF) is the predominant type. Although traditional cardiovascular risk factors are overrepresented in RA patients, they alone do not sufficiently explain higher morbidity. Chronic inflammation is a suspected contributor to myocardial dysfunction. Further data is necessary to elucidate the influence of persistent RA disease activity and RA treatment on HFNEF. Objectives To correlate clinical signs, laboratory findings and echocardiographic markers of heart failure in a well-characterized cohort of RA-patients with cardiovascular risk factors and comorbidity Methods Prospective cross-sectional study including all RA-patients consecutively treated in our community based outpatient-clinic in a 3 months period. Inclusion criteria were written consent and diagnosis of RA, fulfilling ACR/EULAR-criteria. All patients were interviewed using a standardized questionnaire. Clinical signs were evaluated based upon Framingham criteria. Laboratory tests included NT-proBNP. Echocardiography contained tissue doppler and global longitudinal strain (GLS) imaging. Results 162 patients with RA, n=110 (68%) female, mean (SD) age 61.3 (±13.1) years, mean disease duration 12.5 (±11.4) years, mean DAS 28 2.8 (±1.0), mean FFbH 68 (±27)%, mean HAQ 1.3 (±0.9) were included. Rate of remission or low-disease-activity (DAS 28 and lower remission rates in the biologic groups according to more severe disease state and longer disease duration. However, no significantly differences were found for HFNEF rates and cardiovascular comorbidity. Conclusions Traditional risk factors as well as RA-related factors are responsible for HFNEF in RA. RA-duration, persistent disease activity with DAS 28 >2.6, increased ESR as markers of chronic inflammation were shown to be significant and independent contributors. The reduced GLS in HFNEF patients supports a putative role of endomyocardial fibrosis as a link between inflammation and impaired myocardial function. Disclosure of Interest None Declared

Mercury concentrations in morning urine and ejaculate were detected in 80 husbands of women presenting for infertility treatment. Additionally, the number of their dental amalgam fillings was documented. A routine spermiogram was performed, from which a numerical "fertility index" was calculated. Urinary mercury concentrations were in the range of non-exposed populations, only minute Hg concentrations were determined in ejaculate, 75% of the semen sample concentrations were under the detection limit of 5 micrograms/l. In comparison, 7 proven fertile workers with occupational mercury exposure had elevated levels of mercury in their ejaculates (range 10-65 micrograms/l). No positive correlation could be established between subject mercury concentrations in urine or ejaculate and the quality of their semen, expressed as fertility index. Equally, no such correlation could be established between the fertility index and the number of their dental amalgam fillings. From these preliminary data no evidence can be derived for the alleged relation between the mercury burden from dental amalgam fillings and male fertility disorders.

Methylazoxymethanol (MAM) is an alkylating agent that is used to induce microencephaly by killing mitotically active neuroblasts. We found that at later developmental times, MAM exposure can result in abnormal fiber growth in vivo. However, there have not been any previous studies on the effects of MAM on differentiating neurons. We examined the outcome of short exposure to MAM on postmitotic embryonic hippocampal cultures during the establishment of axonal polarity. At 0, 1, or 2 days in vitro (DIV), neurons were treated with 0.1 nM-1 microM MAM for 3 hr and then transferred to glial conditioned media. At 3 DIV, the cells were fixed and analyzed by immunofluorescent staining for neuron viability and differentiation. Control cells initiate several minor processes; one process elongates rapidly at about 1 DIV eventually becoming an axon, while extensive dendritic growth occurs after 3-4 DIV. Neurons treated with 1 microM MAM at 0 or 1 DIV showed a marked inhibition of neurite growth and withdrawal of axons without affecting cell viability. These cells continued to show minimal neurite outgrowth at 7 DIV, even when transferred to a glial coculture. In contrast, cells treated initially with MAM, after neuronal polarity is established at 2 DIV, showed no effect on axonal growth. To determine the effects of MAM on the neuronal cytoskeleton, we examined the in vitro assembly of brain microtubules in a one cycle assay. Exposure to MAM depleted the soluble pool of proteins, including microtubule-associated protein 1B (MAP1B) and MAP2, which are required for neurite outgrowth, through a nonspecific process. Under non-saturating conditions, there were no changes in the total amount of microtubules assembled or the coassembly of MAP1B and MAP2 in the presence of MAM. These results demonstrate that MAM can directly affect differentiating neurons, indicating that an early disruption of axonal outgrowth may have long-term effects.

The molecular organization in lamellar mesophases was proposed on the basis of dynamic and static light scattering, polarizing and transmission electron microscopy, and X-ray diffraction measurements. The basic symmetries of the dynamics of formation and structures of the lamellar bilayers and multilayers of the surfactants of alkylbenzenesulphonate series were found to be consistent from the beginning of the precipitation process from a homogeneous solution until the aggregation to the macroscopic aggregates, due to the self-similarity. The molecular organization in lamellar mesophases was proposed on the basis of dynamic and static light scattering, polarizing and transmission electron microscopy, and X-ray diffraction measurements. The basic symmetries of the dynamics of formation and structures of the lamellar bilayers and multilayers of the surfactants of alkylbenzenesulphonate series were found to be consistent from the beginning of the precipitation process from a homogeneous solution until the aggregation to the macroscopic aggregates, due to the self-similarity.

An emerging goal of fs pump-probe spectroscopy is the study of chemical reaction dynamics of polyatomic molecules and it is important to develop methods for their study. We describe such an experiment by S(t) = ||2 where S(t) is the measurement, |f> is the final state, used as a 'template' onto which we project the dynamics, μ(Q) is the coordinate dependent dipole coupling, and |ex(t)> is the wavepacket that we wish to study. In general, the choice of the final state |f> must take into consideration several effects: (1) In order to decompose the evolving wavepacket in the basis of the final states, |f> must be well known (unfortunately, higher excited states of polyatomic molecules are poorly known); (2) Variation of the dipole coupling between electronic states during the wavepacket evolution (i.e. due to non-adiabatic effects) will have a strong effect on the measured signals. It is important to choose a technique which 'follows' the reaction dynamics, even to 'dark' states. (3) Polyatomic reaction dynamics implies multidimensional wavepackets with many frequency components.

Microtubule-associated proteins (MAPs), such as tau, modulate neuronal shape and process outgrowth by influencing the stability and organization of microtubules. The dynamic nature of MAP-microtubule interactions in vivo, however, is poorly understood. Here, we have assessed the stability of these interactions by investigating the synthesis and axoplasmic transport of tau in relation to that of tubulin and other MAPs within retinal ganglion cells of normal adult mice in vivo. Using immunoprecipitation and Western blot analysis with anti-tau monoclonal and polyclonal antibodies, we unequivocally identified in optic axons a family of 50–60 kDa tau isoforms and a second 90–95 KDa tau family, the members of which were shown to contain the domain of tau encoded by exon 4A. To measure the rates of translocation of tau proteins in vivo, we injected mice with 35S- methionine intravitreously and, after 6–30 d, quantitated the radiolabeled tau isoforms immunoprecipitated from eight consecutive 1.1 mm segments of the nerve and optic tract and separated by electrophoresis. Linear regression analysis of protein transport along optic axons showed that the tau isoforms advanced at a rate of 0.2–0.4 mm/d, and other radiolabeled MAPs, identified by their association with taxol-stabilized microtubules, moved three- to fivefold more rapidly. By contrast, tubulins advanced at 0.1–0.2 mm/d, significantly more slowly than tau or other MAPs. These studies establish that tau is not cotransported with tubulin or microtubules, indicating that associations of tau with microtubules within axons are not as stable as previously believed. Our findings also reveal differences among various MAPs in their interactions with microtubules and provide evidence that assembly and reorganization of the microtubule network is an active process even after axons establish connections and fully mature.

The aim of this study was to assess whether a screening program for fetal cardiac malformations is justified in a low-risk population, and which factors influence its accuracy. The fetal heart was evaluated in 7024 pregnant women at 20-22 weeks, and evaluation was repeated at a more advanced gestational age in 9% of cases. Cardiological follow-up was continued postnatally until 2 years of age. The overall prevalence of cardiac anomaly was 0.93%. The incidences of major and minor defects were 0.44% and 0.48%, respectively. There were 23 true positives (0.33%): in 20 cases, the diagnosis was made in the second trimester, and 13 women (65%) chose termination of pregnancy. Seventeen of the 20 cases identified in the second trimester were serious malformations. There were 42 false negatives (0.60%). Of these, 12 had signs of cardiac dysfunction at birth or within the 1st month of life, and three of them died as a result of their cardiac anomaly. There were eight false positives (0.11%), all of a minor type. Six abnormal karyotypes, out of a total of 21 performed in the true-positive group (28.5%), were found. In addition, five of the 42 newborns in the false-negative group had trisomy 21. The overall sensitivity was 35.4%, and 61.3% for major defects. The accuracy in two distinct periods was estimated because the level of experience of the operators was different: sensitivity was 45.2% in period 1 (1986-88) (77.8% for major defects) and 26.5% in period 2 (1989-92) (52.9% for major defects). We conclude that a fetal heart screening program in the obstetric population is justified. It defines a high-risk group for karyotyping, allows planning of delivery in a tertiary center or the choice of terminating the pregnancy for the parents and appears to have a positive cost-benefit ratio. A crucial factor is the level of training and experience of the operators, who need specific teaching support.