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Resume La litterature sur le pere permet de definir la preoccupation paternelle primaire comme etant un etat psychique particulier du pere durant la periode perinatale. Grâce a des processus identificatoires, le pere fait preuve d’une souplesse psychique lui permettant de s’accorder aux besoins de son enfant. Afin d’eprouver et de completer cette definition, quatre familles ont ete rencontrees a deux reprises du septieme mois de grossesse aux trois mois du bebe. Les resultats de la methodologie experimentale et qualitative qui a ete utilisee (IRPAG/Entretien R/LTP) montrent que cette conscience paternelle se developpe dans l’identite paternelle pour s’orienter ensuite vers l’enfant, dans un systeme intersubjectif triadique. Cette recherche ouvre sur la necessite de considerer le bien-etre du pere dans la dynamique familiale.

Two trials were conducted with 48 newly weaned piglets (28 d old) each 8.6 ± 0.05 kg to study how

The volume production of industrial hydrogel sensors lacks a quality-assuring manufacturing technique for thin polymer films with reproducible properties. Overcoming this problem requires a paradigm change from the current recipe-driven manufacturing process to a specification-driven one. This requires techniques to measure quality-determining hydrogel film properties as well as tools and methods for the control and optimization of the manufacturing process. In this paper we present an approach that comprehensively addresses these issues. The influence of process parameters on the hydrogel film properties and the resulting sensor characteristics have been assessed by means of batch manufacturing tests and the application of several measurement techniques. Based on these investigations, we present novel methods and a tool for the optimization of the cross-linking process step, with the latter being crucial for the sensor sensitivity. Our approach is applicable to various sensor designs with different hydrogels. It has been successfully tested with a sensor solution for surface technology based on PVA/PAA hydrogel as sensing layer and a piezoelectric thickness shear resonator as transducer. Finally, unresolved issues regarding the measurement of hydrogel film parameters are outlined for future research.

Background and Purpose— Strokes have especially devastating implications if they occur early in life; however, only limited information exists on the characteristics of acute cerebrovascular disease in young adults. Although risk factors and manifestation of atherosclerosis are commonly associated with stroke in the elderly, recent data suggests different causes for stroke in the young. We initiated the prospective, multinational European study Stroke in Young Fabry Patients (sifap) to characterize a cohort of young stroke patients. Methods— Overall, 5023 patients aged 18 to 55 years with the diagnosis of ischemic stroke (3396), hemorrhagic stroke (271), transient ischemic attack (1071) were enrolled in 15 European countries and 47 centers between April 2007 and January 2010 undergoing a detailed, standardized, clinical, laboratory, and radiological protocol. Results— Median age in the overall cohort was 46 years. Definite Fabry disease was diagnosed in 0.5% (95% confidence interval, 0.4%–0.8%; n=27) of all patients; and probable Fabry disease in additional 18 patients. Males dominated the study population (2962/59%) whereas females outnumbered men (65.3%) among the youngest patients (18–24 years). About 80.5% of the patients had a first stroke. Silent infarcts on magnetic resonance imaging were seen in 20% of patients with a first-ever stroke, and in 11.4% of patients with transient ischemic attack and no history of a previous cerebrovascular event. The most common causes of ischemic stroke were large artery atherosclerosis (18.6%) and dissection (9.9%). Conclusions— Definite Fabry disease occurs in 0.5% and probable Fabry disease in further 0.4% of young stroke patients. Silent infarcts, white matter intensities, and classical risk factors were highly prevalent, emphasizing the need for new early preventive strategies. Clinical Trial Registration Information— URL: http://www.clinicaltrials.gov .Unique identifier: NCT00414583

Summary Specific pathogen-free chickens were infected with a clonal culture of the protozoan parasite, Histomonas meleagridis. Severe lesions were found within the caeca of all birds euthanized at 7 and 14 days post-infection (d.p.i.). Following necropsy of birds, intestinal samples were taken to establish ex vivo tissue cultures to determine the IgG, IgA and IgM antibody levels in the supernatants before and after incubation with a recently established ELISA. Presence of antibodies was also determined in the sera and first optical density values for IgG above the cut-off were detected at 14 d.p.i. IgA levels remained low in the serum with a small peak 4 weeks p.i., a phenomenon also found for IgM. The intestinal tissue samples showed very strong immunological reactions in the parasitized caeca with an initial peak of IgM, high levels of IgG and a continuous increase of IgA. In the duodena and jejuna, IgA values reached similar high levels as those obtained in the caeca, whereas IgG and IgM increased only slightly.

No serological method suitable for large screening of antibodies against Histomonas meleagridis in poultry is available so far, the objective targeted in the present investigation. Consequently, an ELISA was developed as a suitable tool for this purpose. Investigating serum samples from non-infected specific pathogen-free (spf) chickens and commercial turkeys a high-background signal was noticed when ELISA plates were directly coated with purified parasitic cells. This signal was significantly reduced by coating the plates with a polyclonal rabbit antibody, raised against histomonads, prior to the addition of the antigen. Adopting this approach five antigen preparations were compared and a high reproducibility could be demonstrated reflected by a very low coefficient of variation of 5.3% and 1.7% for the chicken and turkey sera, respectively. After this initial development all further experiments were carried out with one set of plates and the same antigen preparation. Investigating chicken sera obtained from birds infected at 14 days of life, OD values above a predetermined cut-off value were observed 2 weeks post-infection and a rise of IgG antibodies was noticed until 6 weeks post-infection, when the experiment was terminated. Non-protected turkeys infected at 6 weeks of age displayed an increasing IgG response until 14 days post-infection, prior to the death of animals due to histomonosis. In comparison, the majority of turkeys vaccinated with attenuated histomonads, obtained through prolonged passaging and challenged 4 weeks later with virulent parasites, displayed a demonstrable antibody response after the challenge only. Antibody titres increased until 4 weeks post-challenge when the birds were killed and the study was terminated. Altogether, the developed indirect sandwich ELISA proved to be a quick and efficient method to detect IgG antibodies against H. meleagridis in sera of experimentally infected chickens and turkeys and will be a helpful tool to obtain more insights into the epidemiology of the parasite and the immune response of its hosts.

Background and purpose: We evaluated the effects of 1-(3′,4′-dichloro-2-fluoro[1,1′-biphenyl]-4-yl)-cyclopropanecarboxylic acid (CHF5074), a new γ-secretase modulator, on brain β-amyloid pathology and spatial memory in transgenic mice expressing the Swedish and London mutations of human amyloid precursor protein (hAPP). Experimental approach: Sixty 6-month-old hAPP mice were treated for 6 months with CHF5074 or ibuprofen (375 ppm in the diet) or standard diet. Twenty-one wild-type mice received standard diet. Key results: Compared with transgenic controls, CHF5074 treatment significantly reduced the area occupied by plaques in cortex (P = 0.003) and hippocampus (P = 0.004). The number of plaques were also reduced by CHF5074 in both cortex (P = 0.022) and hippocampus (P = 0.005). Plaque-associated microglia in CHF5074-treated animals was lower than in transgenic controls in cortex (P = 0.008) and hippocampus (P = 0.002). Ibuprofen treatment significantly reduced microglia area in cortex and hippocampus but not β-amyloid burden. On the last day of the Morris water maze, transgenic controls performed significantly worse than the non-transgenic animals and the CHF5074-treated transgenic mice, on the swimming path to reach the hidden platform. Ibuprofen-treated animals did not perform significantly better than transgenic controls. Conclusions and implications: Chronic CHF5074 treatment reduced brain β-amyloid burden, associated microglia inflammation and attenuated spatial memory deficit in hAPP mice. This novel γ-secretase modulator is a promising therapeutic agent for Alzheimer's disease.

An extracorporeal procedure is described for the selective removal of LDL from patients with familial hypercholesterolemia. It comprises plasmapheresis followed by selective precipitation of LDL from plasma with heparin at low pH. The LDL-heparin complex is then removed by filtration and the clear plasmafiltrate subjected to bicarbonate dialysis to restore physiological pH and maintain fluid and electrolyte balance. The capacity and efficiency of the system for the selective elimiation of LDL was confirmed by in vitro studies with three liters of plasma from a hypercholesterolemic patient. Extensive animal investigations have demonstrated the applicability and biocompatibility of the procedure. This has been further confirmed by a first application in a human volunteer.

The implementation challenge for new low-cost low-power wireless modem transceivers has continuously been growing with increased modem performance, bandwidth, and carrier frequency. Up to now we have been designing transceivers in a way that we are able to keep the analog (RF) problem domain widely separated from the digital signal processing design. However, with today’s deep sub-micron technology, analog impairments – “dirt effects” – are reaching a new problem level which requires a paradigm shift in the design of transceivers. Examples of these impairments are phase noise, non-linearities, I/Q imbalance, ADC impairments, etc. In the world of “Dirty RF” we assume to design digital signal processing such that we can cope with a new level of impairments, allowing lee-way in the requirements set on future RF sub-systems. This paper gives an overview of the topic and presents analytical evaluations of the performance losses due to RF impairments as well as algorithms that allow to live with imperfect RF by compensating the resulting error effects using digital baseband processing.

Li and colleagues summarized the most frequently used Alzheimer's disease (AD) mouse models available for drug testing and the mediating effects of the different compounds. With almost 300 cited publications, authors present the research community's effort of the last 10 years in finding a new drug for the treatment of AD. Some of the transgenic mouse lines mentioned by Li and colleagues are discussed only very briefly. Since we are convinced that a couple of these models indeed have a great value for AD research and the development of new AD drugs we will subsequently describe a few of them in more detail. A suitable mouse model of AD does not only have to mimic major hallmarks of AD that are modifiable by different test substances as mentioned by the authors; they also have to be translational to clinical trials in humans. For the following discussion, we will therefore also include information on clinical trials of drugs previously tested in the different transgenic mice.

Introduction DKI by measuring non-Gaussian diffusion may better characterize the microstructural brain changes as compared to traditional DTI. The aim was to evaluate the capability of DKI for detecting the microstructural changes induced by alpha-synuclein accumulation in TNWT-61 mice using the tract based spatial statistics (TBSS) and region of interest (ROI) analyses. Methods Fourteen month old TNWT-61 mice and wild-type (WT) littermates underwent DKI scanning using 9.4 Tesla MRI system in vivo. TBSS and ROI analysis was performed to detect the changes in white and gray matter in TNWT-61 and WT mice. Immunohistochemistry for alpha-synuclein was performed in 5 TNWT-61 mice and correlated with DKI findings. Results The principle findings of this study were increase in mean kurtosis and decrease in mean diffusivity in thalamus, sensorimotor cortex, hippocampus, external capsule and basolateral amygdaloid nucleus in 14 month TNWT-61 mice as compared to WT littermates. We also found significant correlations between alpha-synuclein accumulation and increase in kurtosis and decrease in diffusivity in the thalamus. Conclusion Our results reveal that DKI is sensitive in detecting microstructural changes due to alpha-synuclein accumulation in both GM and WM. These findings suggest that in PD patients DKI should be preferred to routine DTI despite a longer acquisition protocol.

The boosters of ARIANE 5 are currently made of 7 rings of the high strength steel 48 CrMoNiV 4 10 (D6AC) jointed together by a Clevis Tang technique. In a future design the rings could be jointed by electron beam welding. This paper represents first results of a qualification program of this new technique. Especially, the influence of stress triaxiality on fracture behaviour of the weld metal is characterized by testing different fracture mechanics specimens, e.g. tension and bending specimens with different crack lengths and crack forms. To find the relation between global and local behaviour all experiments were simulated using the corresponding material data for different material zones. Since the weld metal fails by brittle fracture, a two-parameter concept with J c and a parameter describing the stress triaxiality was applied for the assessment of the weld joints. Additionally, the RKR-model was used as local concept. Based on the results of the specimens the loading situations of a booster under operating loading were analysed for two assumed crack positions.

In the course of an ARIANE 5 evolution program, the booster cases made of 48 CrMoNiV 4 10 high strength, low alloy steel will be modified such that 6 of the shear bolt connections will be replaced by EB-welds as illustrated in Fig. 1. The introduction of welds has been chosen to achieve the following goals: • Mass reduction • Cost reduction • Increase of reliability • Simplification of thermal insulation application The concept of the damage tolerance verification which is in progress for justification of the improved booster cases is presented. By a very detailed local approach based on the characterization of the properties and the mechanical behaviour of the different zones of a weld seam, the overall damage tolerance of the weld shall be derived. The achieved prediction model has been verified by different component tests and will finally be qualified by a full scale qualification test.

The effects of the peptidergic nootropic drug Cerebrolysin on spatial memory and motor activity were examined in intact and ischemic rats. Ischemic-hypoxic damage was induced by injection of Na-cyanide followed by bilateral occlusion of common carotid arteries. Immediately afterwards Cerebrolysin or saline was administered, either by continuous intraventricular (i.v.) infusion or by daily intraperitoneal (i.p.) injection. Rats were tested for spatial memory and motor activity in the Morris water maze on days 3 and 4 post-surgery. The best dose of the substance for i.p. administration was known from previous studies. Therefore we had to investigate the dose-response-relationship and tolerability of the drug after i.v. administration in intact rats. Infusion (i.v.) of a high dose of Cerebrolysin (0.57 mg/day) decreased motor activity and spatial memory of intact rats (p0.01 and p0.05, respectively) but low dose of Cerebrolysin was well tolerated in the intact animals. Ischemia led to deterioration of motor activity in control rats (p0.01). Cerebrolysin significantly counteracted deleterious motor changes due to ischemia up to the level of intact controls after both i.v. infusion (0.0057 mg/day) and daily i.p. drug administration (100 mg/kg bw and day) indicating an accelerating recovery after ischemia.

Members of the nerve growth factor (NGF) family of neurotrophins bind to the second leucine-rich motif (LRM2) within the extracellular domains of their respective receptors (trkA, trkB, trkC). Small LRM2 peptides have been recently demonstrated to selectively bind the neurotrophins revealing similar complex binding characteristics as full-length receptors. We extend our recent findings, showing that the peptides (A and C) do not block nerve fiber outgrowth through high affinity trk receptors in a ganglia bioassay. Since the highest concentration of neurotrophins [NGF, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3)] is found in the hippocampus, the peptides were injected into the 3rd ventricle of anesthetized adult rats. The (NGF binding) LRM2-A peptide, but not the (BDNF binding) LRM2-B or the (NT-3 binding) LRM2-C peptides, caused severe apoptotic neurodegeneration of hippocampal pyramidal CA1 neurons as revealed by cresyl violet staining and the TUNEL reaction. The degeneration was protected by intrahippocampal injection of NGF-beta and by the non-N-methyl-D-aspartate (NMDA) antagonist CNQX (6-cyano-7-nitroquinoxaline-2,3-dione), indicating a glutamatergic mechanism. In situ hybridization revealed that pyramidal CA1 neurons did not express trkA and p75 receptor mRNA in sham and LRM2-A-lesioned animals. It is concluded that the LRM2-A peptide represents a novel peptide with properties to induce apoptotic cell death of pyramidal CA1 neurons and may be useful as an experimental agent.

Low oxygen tension exerts a significant effect on the replication of several DNA and RNA viruses in cultured cells. In vitro propagation of hepatitis C virus (HCV) has thus far been studied under atmospheric oxygen levels despite the fact that the liver tissue microenvironment is hypoxic. In this study, we investigated the efficiency of HCV production in actively dividing or differentiating human hepatoma cells cultured under low or atmospheric oxygen tensions. By using both HCV replicons and infection-based assays, low oxygen was found to enhance HCV RNA replication whereas virus entry and RNA translation were not affected. Hypoxia signaling pathway-focused DNA microarray and real-time quantitative reverse transcription-PCR (qRT-PCR) analyses revealed an upregulation of genes related to hypoxic stress, glycolytic metabolism, cell growth, and proliferation when cells were kept under low (3% [vol/vol]) oxygen tension, likely reflecting cell adaptation to anaerobic conditions. Interestingly, hypoxia-mediated enhancement of HCV replication correlated directly with the increase in anaerobic glycolysis and creatine kinase B (CKB) activity that leads to elevated ATP production. Surprisingly, activation of hypoxia-inducible factor alpha (HIF-alpha) was not involved in the elevation of HCV replication. Instead, a number of oncogenes known to be associated with glycolysis were upregulated and evidence that these oncogenes contribute to hypoxia-mediated enhancement of HCV replication was obtained. Finally, in liver biopsy specimens of HCV-infected patients, the levels of hypoxia and anaerobic metabolism markers correlated with HCV RNA levels. These results provide new insights into the impact of oxygen tension on the intricate HCV-host cell interaction.

There has been an extensive discussion in the forensic toxicology community regarding the effect of trauma on the enzymatic method for ethanol analysis. There is a paucity of information in the literature that addresses this question. This study was designed to compare the Dade Behring Dimension enzymatic method with the reliable gas chromatographic method. The blood samples collected at the same time from trauma patients were analyzed by both methods. The result of the study shows no significant quantitative difference between the enzymatic and gas liquid chromatographic (GLC) methods. Also, the enzymatic method did not show any false positive ethanol in cases where the GLC method showed a negative finding.

A feasibility study was undertaken to evaluate laboratory phlebotomists performing bedside glucose monitoring (BGM) over a 3-month period on a medical and surgical floor. Specific questions included: feasibility of providing testing on a 24-h basis, accuracy, appropriate utilization, effect on patient care, and an analysis of cost. In all, 1975 tests were performed on 114 patients. BGM results were within 15% of the laboratory's result 97% of the time. Patient and physician satisfaction was high. Although the cost of BGM is slightly higher than a laboratory glucose test, its use appeared to reduce the length of hospital stay by 0.47 days. Practical information on initiating a highly successful BGM program is provided.

Calculations are presented of the electronic structure of a hierarchy of rational approximants to icosahedral AlPdMn quasicrystals. A model for the atomic structure has been constructed via the projection method, using atomic surfaces appropriate to reproduce the diffraction patterns of the icosahedral phase. The electronic structure has been calculated self-consistently in the local-density approximation using the linear-muffin-tin-orbital (LMTO) method and tight-binding LMTO techniques. It is shown that the electronic density of states of the higher-order approximants is characterized by a structure-induced pseudogap at the Fermi-level. However, unlike the case for most quasicrystals investigated so far, no corresponding pseudogap exists for the lowest-order approximants.

The state-of-the art of computational studies of dynamical properties of quasicrystalline and amorphous alloys is reviewed. It is shown that the properties of propagating collective excitations in both quasicrystals and glasses are dominated by ‘quasi’- or ‘pseudo-Brillouin zone’ effects, with the most intense Bragg reflections of the quasicrystal or the main peak in the static structure factor of the glass playing a role of analogous to the Γ-points in the reciprocal lattice of a crystal. It is shown that localized modes exist in both glasses and quasicrystals. However, by contrast with glasses where localization appears only at the edges of the vibrational spectrum, in quasicrystals localized modes exist also at intermediate frequencies and interesting correlations with the topological properties of the quasilattice can be established.

The extracellular domains of the TrkA nerve growth factor (NGF) receptor and its homologs harbor a modular mosaic of potential ligand binding motifs, namely two immunoglobulin (Ig)-like modules and an LRM3 cassette consisting of a tandem array of three leucine-rich motifs (LRMs) flanked by cysteine-rich clusters (Schneider, R., and Schweiger, M. (1991) Oncogene 6, 1807-1811). Identification of a structural motif capable of specifically recognizing the various neurotrophins was achieved by assessing their affinities to isolated recombinant modules of TrkA and TrkB. In both receptors the LRM3 cassette alone could mediate the respective neurotrophin selectivities and affinities. Further tracking down of this NGF-binding site in TrkA strikingly revealed that a single LRM of 24 amino acids could bind NGF selectively with nanomolar affinity. Since this is the first example of a single LRM with a highly specific, well defined function, it might serve as a valuable tool to elucidate the general structural requirements of substrate recognition and high affinity binding in the large superfamily of LRM-containing proteins.

TrkB is a member of the Trk family of neurotrophin receptors. Its extracellular domain exhibits the same modular structure found in its homologs, TrkA and TrkC, consisting of an N-terminal LRM3 cassette and two immunoglobulin-like modules (Ig2 domain) adjacent to the membrane. The LRM3 cassette comprises two cysteine-rich clusters framing a tandem array of three leucine-rich motifs (LRMs). On the basis of the recent identification of a nerve growth factor (NGF) binding site within TrkA, the ability of the different structural entities within the extracellular domain of TrkB to bind the various neurotrophins was determined by using a recombinant receptor approach. Brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4) bound to the LRM3 cassette of TrkB, whereas NGF did not. These binding characteristics evidently reflect in vivo specificities. A more precise mapping of the region(s) responsible for binding BDNF, NT-3, and NT-4 identified the second leucine-rich motif of TrkB as a functional unit capable of binding all three neurotrophins. The affinities and kinetics that this short stretch of amino acids exhibited with respect to the different neurotrophins were clearly akin to those observed for cells ectopically expressing TrkB receptors. With 24 amino acids determining the affinities and kinetics of the interactions with three different partners, the leucine-rich motif is strongly established as one of the most potent and flexible protein--protein interaction motifs.

The electronic structure has been calculated for large approximant crystals (up to 51752 atoms in the periodically repeated cell) to icosahedral AlCuLi quasicrystals. The results show that a deep structure-induced pseudogap at the Fermi energy is a generic property of the quasicrystal and its crystalline approximants. The physical mechanism for the formation of the gap is discussed on the basis of a quasiperiodic generalization of the nearly-free-electron model.

Serum samples from 1120 layers from 56 flocks and 400 pullets from 20 flocks were tested by an indirect sandwich ELISA to investigate the prevalence of antibodies to Histomonas meleagridis in chickens kept in alternative husbandry systems. The overall prevalence of antibodies to H meleagridis in layers was 37.3 per cent, and positive birds were identified in 50 flocks. This was significantly higher than in pullets, where only 8.3 per cent of the birds tested positive. Optical density (OD) values obtained from pullet sera were much lower than the OD values from layers; however, positive birds were detected in half of the pullet flocks. In particular, all birds from an organic pullet flock were found to be positive, with high OD values. Overall, the highest prevalence of positive sera was obtained from birds kept in free-range flocks. Attempts to reisolate live histomonads from birds in 18 layer flocks were unsuccessful.

The structure and stability of icosahedral AlCuLi(Mg) alloyhas been investigated using molecular-dynamics simulations. The structural model is based on a 3D Penrose tiling with a slightly modified Henley-Elser decoration. Large periodic approximants of the quasicrystal (with more than 12000 atoms per cell) have been subjected to an isothermal molecular dynamics annealing with pseudopotential-derived interatomic forces. It is found that the quasicrystalline structure is stable, but the interatomic forces lead to a displacive modulation of the idealized structure. The calculated total and partial pair-correlation functions and diffraction patterns are in very good agreement with experiment; the analysis of the diffraction intensities yields a reliability-factor R ∼ 0.13.

One-day-old turkey poults were vaccinated against histomonosis (syn. histomoniasis) via the oral route by application of in vitro attenuated Histomonas meleagridis. Subsequently, two different groups composed of 14 birds each were challenged cloacally with highly virulent histomonads after 2 or 4 weeks. Two additional groups of non-vaccinated birds were infected with the challenge inoculum at the same time points. In addition, a group of 19 birds, of which 14 were vaccinated but not challenged, were kept for clinical and serological examinations. Non-vaccinated and non-challenged birds (n=10) represented the negative control group. All non-vaccinated but infected birds and 10 out of 14 vaccinated turkeys challenged 2 weeks post vaccination (w.p.v.) contracted severe histomonosis. Turkeys challenged 4 w.p.v. and all remaining birds used in this experiment did not show any pathognomonic clinical signs. In addition, no adverse effect regarding the weight gain could be observed in birds that were vaccinated but not challenged. The excretion of attenuated and virulent live histomonads was observed very infrequently by re-isolation, but transmission to in-contact birds was very efficient. Presence of antibodies was first noticed 3 w.p.v. and antibody levels remained above the cut-off value until termination of the experiment at 16 w.p.v. The present experiment demonstrates for the first time the potential efficacy of in vitro attenuated histomonads used as an orally applied vaccine to 1-day-old turkeys for protection against fatal histomonosis without affecting performance.

Specific pathogen-free chickens were infected with a clonal culture of the protozoan parasite, Histomonas meleagridis. Severe lesions were found within the caeca of all birds euthanized at 7 and 14 days post-infection (d.p.i.). Following necropsy of birds, intestinal samples were taken to establish ex vivo tissue cultures to determine the IgG, IgA and IgM antibody levels in the supernatants before and after incubation with a recently established ELISA. Presence of antibodies was also determined in the sera and first optical density values for IgG above the cut-off were detected at 14 d.p.i. IgA levels remained low in the serum with a small peak 4 weeks p.i., a phenomenon also found for IgM. The intestinal tissue samples showed very strong immunological reactions in the parasitized caeca with an initial peak of IgM, high levels of IgG and a continuous increase of IgA. In the duodena and jejuna, IgA values reached similar high levels as those obtained in the caeca, whereas IgG and IgM increased only slightly.

During long-term treatment with amiodarone, slowing of conduction through the atrioventricular node, a prolongation of the QT-interval, and a prolongation of the atrial and ventricular myocardial refractoriness always developed. During short-term treatment, these effects were not found, except for depression of the AV-nodal conduction. This led to the suggestion that the electrophysiological effects of amiodarone during long-term treatment might be partly the result of the accumulation of its metabolite desethylamiodarone. Therefore, we examined the electrophysiological effects of amiodarone and desethylamiodarone on conduction and refractoriness in isolated spontaneously beating guinea pig hearts perfused by the method of Langendorff. Within 1 h of perfusion, desethyl-amiodarone caused a more pronounced prolongation of the AV-nodal, His-bundle, and intraventricular conduction intervals than did amiodarone. Desethylamiodarone, but not amiodarone led to a prolongation of the QT-interval. The refractoriness of sinoatrial-, AV-nodal conduction, and of the atrial myocardium were significantly more prolonged by amiodarone than by desethylamiodarone. Both compounds showed a comparable strong rate-dependent effect on AV-nodal refractoriness. The ventricular refractoriness was similarily prolonged by either compound. These results show that for the class-III effects (i.e., prolongation of repolarization period) observed under chronic treatment of amiodarone the metabolite desethylamiodarone may be responsible. Desethylamiodarone also exerts more pronounced effects on the fast-channel-dependent parts of the conduction system than does amiodarone, a fact indicated by a higher prolongation of His-bundle and intraventricular conduction.

Alpha-synuclein is the main constituent of intra-neuronal Lewy bodies, which are characteristic of Parkinson's disease, but aggregates are also found as axonal inclusions. Alpha-synuclein pathology is found together with beta-amyloid plaques and neurofibrillary tangles in Alzheimer's disease and other neurodegenerative disorders. In spite of the fact that the biological function of this synaptic protein is not known so far, there is an increasing body of evidence indicating an interaction with amyloid peptides, but also with tau-hyperphosphorylation. A high proportion of alpha-synuclein purified from Lewy bodies is phosphorylated on Ser129. There are still different opinions about the toxicity of the alpha-synuclein aggregates. Alpha-synuclein seems to influence different intracellular signaling pathways which are in direct relation to defense mechanisms against reactive oxygen species or apoptosis. It is obvious that overproduction of alpha-synuclein, but also different mutations, are inducing the formation of aggregates. Because of the possible link to neurodegeneration, different attempts have been made to counteract alpha-synuclein aggregation. An interesting approach is utilizing beta-synuclein, a biological factor, with an aminoacid sequence closely resembling that of alpha-synuclein. Proof of concept studies indicated that overexpression of beta-synuclein is able to counteract alpha-synuclein aggregation in a transgenic animal model, while also ameliorating functional deficits. As an alternative approach, the use of low molecular beta-synuclein N-terminal peptide derivatives has been considered. Several of these structures displayed clear neuroprotective activities in tissue culture models of neurodegeneration, including beta-amyloid toxicity. Therefore it has been speculated that these compounds might have a broad therapeutic efficacy in different neurodegenerative disorders. A proof of concept study in hAPP-transgenic animals resulted in a highly significant decrease in beta-amyloid plaque load, an increase in soluble beta-amyloid peptides and a decrease in insoluble forms. There was also significant improvement of cognitive deficits in this APP transgenic mouse model following intranasal but also peripheral treatment with three of these compounds. From this study it is concluded that the observed effects of the peptides derived from beta-synuclein N-terminus are depending on both, a direct interaction with aggregation of proteins, but also with stimulation of anti-apoptotic and anti-oxidative intracellular signaling pathways.

The implementation challenge for new low-cost low-power wireless modem transceivers has continuously been growing with increased modem performance, bandwidth, and carrier frequency. Up to now we have been designing transceivers in a way that we are able to keep the analog (RF) problem domain widely separated from the digital signal processing design. However, with today's deep sub-micron technology, analog impairments-dirt effects-are reaching a new problem level which requires a paradigm shift in the design of transceivers. Examples of these impairments are phase noise, non-linearities, IQ imbalance, ADC impairments, etc. In the world of dirty RF we assume to design digital signal processing such that we can cope with a new level of impairments, allowing lee-way in the requirements set on future RF sub-systems. This paper gives an overview of the topic and presents analytical evaluations of the performance losses due to RF impairments as well as algorithms that allow to live with imperfect RF by compensating the resulting error effects using digital baseband processing

Reliable definition of the phenotype of particular alleles is carried out in the genetic background of inbred strains. Appearance of mutations in outbred mice therefore requires the generation of congenic mice. The aim of this study was the establishment of a list of polymorphic microsatellite markers which can be used in a polymerase chain reaction (PCR)-based marker-assisted selection protocol (MASP) to allow the use of the two common outbred stocks, CFW and ICR, as donor animals for the fast generation of congenic C57BL/6 mice. The selection of informative microsatellite markers was carried out to provide a simple evaluation of the PCR products by conventional agarose gel electrophoresis. Outbred mice from three suppliers were examined. In total, 153 microsatellite loci were analysed. Here we present 76 and 70 microsatellite markers polymorphic for the outbred ICR and CFW stocks compared to C57BL/6. At least three microsatellite loci per chromosome were chosen as informative markers for the autosomal genome, giving rise to a maximum marker distance of 58 cM. Thus, additional individual markers have to be selected for the respective outbred mouse which is chosen as a donor animal.

The rejection of the image signal is a problem inherent to all receiver architectures. One of the benefits of the low-IF receiver is, that image rejection is realized by I/Q signal processing instead of a fixed analog filter, making it highly reconfigurable and cost-efficient. However, unavoidable imbalances between the I- and Q-branch lead to a limited image attenuation. In this paper a novel I/Q imbalance compensation scheme is presented, in which the unknown analog imbalance parameters are estimated digitally without the need for any calibration or training signal. Based on these estimates the interference by the image signal is effectively compensated, upgrading the vulnerable ordinary low-IF receiver to a powerful advanced receiver architecture, where the mean value of the image-to-signal ratio never exceeds a pre-defined maximum value, regardless of the image signal power.

A novel blind I/Q imbalance parameter estimation and compensation scheme for low-IF receivers, which was previously proposed by the authors, is analytically analyzed in this paper. As an outcome, we present an equation for calculating the expected power ratio of image and desired signal after compensation. The excellent performance of the novel compensation scheme, which was so far justified by simulations only, is now substantiated by a solid theory.

For the past 20 years the scientific community and the pharmaceutical industry have been searching for treatments to neutralize the devastating effects of Alzheimer disease (AD). During this period important changes in the etiopathogenic concept of AD have occurred and, as a consequence, the pharmacological approach for treating AD has also changed. During the past 2 decades only 3 drugs for AD have been formally approved by the FDA, although in many countries there are several drugs which are currently used as neuroprotecting agents in dementia alone or in combination with cholinesterase inhibitors. The interest of the pharmaceutical industry has also shifted from the cholinergic hypothesis which led to the development of cholinesterase inhibitors to enhance the bioavailability of acetylcholine at the synaptic cleft to a more "molecular approach" based on new data on the pathogenic events underlying neurodegeneration in AD. In our opinion, the pharmacological treatment of AD should rely on a better understanding of AD etiopathogenesis in order to use current drugs that protect the AD brain against deleterious events and/or to develop new drugs specifically designed to inhibit and/or regulate those factors responsible for premature neuronal death in AD. The most relevant pathogenic events in AD can be classified into main categories: primary events (genetic factors, neuronal apoptosis), secondary events (beta-amyloid deposition in senile plaques and brain vessels, neurofibrillary tangles due to hyperphosphorylation of tau proteins, synaptic loss), tertiary events (neurotransmitter deficits, neurotrophic alterations, neuroimmune dysfunction, neuroinflammatory reactions) and quaternary events (excitotoxic reactions, calcium homeostasis miscarriage, free radical formation, primary and/or reactive cerebrovascular dysfunction). All of these pathogenic events are potential targets for treatment in AD. Potential therapeutic strategies for AD treatment include palliative treatment with nonspecific neuroprotecting agents, symptomatic treatment with psychotropic drugs for noncognitive symptoms, cognitive treatment with cognition enhancers, substitutive treatment with cholinergic enhancers to improve memory deficits, multifactorial treatment using several drugs in combination and etiopathogenic treatment designed to regulate molecular factors potentially associated with AD pathogenesis. This review discusses the conventional cholinergic enhancers (cholinesterase inhibitors, muscarinic agonists), noncholinergic strategies that have been developed with other compounds, novel combination drug strategies and future trends in drug development for AD treatment. Stem-cell activation, genetically manipulated cell transplantation, gene therapy and antisense oligonucleotide technology constitute novel approaches for the treatment of gene-related brain damage and neuroregeneration. The identification of an increasing number of genes associated with neuronal dysfunction along the human genome together with the influence of specific allelic associations and polymorphisms indicate that pharmacogenomics will become a preferential procedure for drug development in polygenic complex disorders. Furthermore, genetic screening of the population at risk will help to identify candidates for prevention among first-degree relatives in families with transgenerational dementia.

In spite of several years of experience with the use of cholinesterase inhibitors for treatment of symptoms of Alzheimer's disease their influence on disease progression remains still unclear. New cholinesterase inhibitors should provide an additional neuroprotective activity, because only substances which stop neuronal death can influence disease progression. New treatment strategies are focusing on amyloid processing, preventing the occurrence of toxic A beta(1-42) peptide. These procedures include the vaccination trials, but their clinical usefulness has to be proven. Also strategies focussing on neurofibrillary pathologies should be explored in detail. Drug development for Alzheimer's disease should include all pathological events associated with neurodegeneration, like oxidative stress, neuroinflammation or disturbances in growth factor signaling. Abnormal protein aggregation as a common feature of different neurodegenerative diseases might also be a promising drug target. Beside beta sheet breakers directed against beta-amyloid deposition the endogenous protein beta-synuclein or derivatives of it might be able to counteract aggregation of alpha-synuclein as well as of amyloid beta protein. Interaction with alpha-synuclein deserves special attention because it might be an early step of synaptic degeneration. Due to the complexity of the disease combination of different drugs might be the most promising way to go. The parallel development of early biological markers should enable intervention in pre-symptomatic disease stages.

We investigated the potential mechanisms through which Cerebrolysin, a neuroprotective noothropic agent, might affect Alzheimer's disease pathology. Transgenic (tg) mice expressing mutant human (h) amyloid precursor protein 751 (APP751) cDNA under the Thy-1 promoter (mThy1-hAPP751) were treated for four weeks with this compound and analyzed by confocal microscopy to asses its effects on amyloid plaque formation and neurodegeneration. In this model, amyloid plaques in the brain are found much earlier (beginning at 3 months) than in other tg models. Quantitative computer-aided analysis with anti-amyloid-beta protein (A beta) antibodies, revealed that Cerebrolysin significantly reduced the amyloid burden in the frontal cortex of 5-month-old mice. Furthermore, Cerebrolysin treatment reduced the levels of A beta(1-42). This was accompanied by amelioration of the synaptic alterations in the frontal cortex of mThy1-hAPP751 tg mice. In conclusion, the present study supports the possibility that Cerebrolysin might have neuroprotective effects by decreasing the production of A beta(1-42) and reducing amyloid deposition.

Afamin, an 87 kDa human plasma glycoprotein with specific binding properties for vitamin E (alpha-tocopherol) was recently characterized (Jerkovic, 1997; Vögele, 1999). In the present study the in vitro effects on neuronal cells of native human Afamin, of Afamin pre-loaded with vitamin E (Afamin+), and of vitamin E were investigated. Isolated cortical chicken neurons were maintained either under apoptosis-inducing low serum conditions or exposed to oxidative stress by the addition of H2O2 or beta-amyloid peptide(25-35). Afamin and vitamin E synergistically enhance the survival of cortical neurons under apoptotic conditions. Furthermore, Afamin alone protects cortical neurons from cell death in both experimental settings. Therefore, the plasma glycoprotein Afamin apparently displays a neuroprotective activity not only by virtue of binding and transporting vitamin E but also on its own.