Investigations into the fatigue crack initiation and propagation behaviour in austenitic stainless steel X5 CrNi 18 9 (1.4301)

Controlled load fatigue-crack growth rate tests were conducted using three point bend type specimens. The austenitic stainless steel X5 CrNi 18 9 (material number 1.4301, similar to AISI 304) was tested. For this high toughness material, the crack initiation and crack propagation is discussed in terms of linear-elastic analysis even for the highest plasticity regime. The curve for the onset of stable crack growth during fatigue starting from a notch is discussed as well as the stable crack growth up to large plasticity. From the standpoint of load controlled fatigue it is indicated that the time between crack initiation and crack length at the ?end of life”? is large.     

Efflux of cyclic GMP from activated human platelets

Activation of human platelets is associated with an increased level of cGMP, when total cGMP in individual samples is measured. However, by discriminating between intracellular and extracellular cGMP we were able to demonstrate that cGMP accumulates in the extracellular space only, whereas the level of intraplatelet cGMP actually decreases. Therefore, during the first minutes of platelet aggregation cGMP is released from the cell, and it thereby escapes hydrolysis by intracellular phosphodiesterases. In contrast, during direct activation of soluble guanylyl cyclase by nitrovasodilators, such as sodium nitroprusside, the newly synthesized cGMP remains mainly inside the cells. Elevation of intracellular calcium and activation of protein kinase C are likely to be involved in promoting cGMP efflux. Our results are discussed in contrast to the general hypothesis that the cGMP increase associated with platelet aggregation may represent a feedback mechanism designed to terminate early events of activating signal transduction. According to our data the apparent cGMP increase results from cGMP release from thrombocytes, rather than soluble guanylyl cyclase activation. This cGMP efflux provides a mechanism of decreasing the intracellular cGMP level upon stimulation with platelet agonists and thus favors platelet activation.     

Analysis experiences using information visualization

Professional analysts deal with a high volume of information and must constantly work to separate out the valuable data. However, analysts have difficulty determining what data is useful without reading or skimming almost all returned documents from a search. This presents them with a difficult tradeoff. Searching information broadly returns hundreds or thousands of documents. We present lessons learned from an observational study of the application of the InSpire visually oriented text exploitation system in an operational analysis environment.     

Secretory immunity in HIV infection

Secretory IgA plays a crucial role in the defense of pathogens at mucosal surfaces. As CD4+ T cells are lost early in the mucosa of human immunodeficiency virus (HIV)-infected patients and as CD4+ T cells play an essential role in the regulation of specific IgA responses to pathogenic agents at mucosal sides, it could be expected that this first line of defense is impaired in HIV-infected patients. Therefore, several studies were undertaken to characterize the humoral immune response at mucosal surfaces. However, the results obtained so far are in part contradictory. For intestinal IgA, reduced, increased and no changes compared to controls were described. The different results may be due to different methods applied. In most studies an abnormal predominance of HIV-specific IgG over IgA response was found in the intestine of HIV-infected patients. Studies on cytomegalovirus-specific intestinal antibodies indicate a complete lack of a specific intestinal IgA response. However, in cryptosporidiosis of HIV-infected patients, diarrhea persists despite a secretory IgA response indicating that other factors are also important for the clearance of this pathogen.     

Immunological and trophical effects of Saccharomyces boulardii on the small intestine in healthy human volunteers

Recently we investigated the mechanisms mediating the transport of valproic acid (VPA) between blood and brain. In one study efflux of valproic acid (VPA) from rabbit brain was inhibited by probenecid. Efflux of VPA decreased when probenecid was given intravenously but not when probenecid was given by ventriculocisternal (VC) perfusion indicating that the major site of probenecid-sensitive transport was at the brain capillary endothelium and not at the choroid plexus. In another study VPA transport into rat brain was inhibited by para-aminohippurate (PAH). The purpose of the present study were to determine (a) if the efflux of VPA from rabbit brain was also inhibited by PAH, and (b) whether efflux of VPA could occur at the choroid plexus via an PAH-selective transport system. Six control rabbits received VPA by intravenous infusion and tracer concentrations of [3H]VPA and [14C]PAH by VC perfusion. Rabbits in the PAH group (n = 6) received identical treatment with VPA, tracer concentrations of [3H]VPA and [14C]PAH and, in addition, received 20 mM PAH by VC perfusion. PAH had no effect on the VC extraction ratio of [3H]VPA or the steady-state brain concentration of intravenously administered VPA. It is concluded that the efflux of VPA at the rabbit blood-brain barrier is mediated by a transporter different from the PAH-like transporter responsible for the uptake of VPA into rat brain. In addition, the finding that VC perfusion with PAH had no effect on the VC extraction of [3H]VPA provides further evidence that the choroid plexus plays a negligible role in removal of VPA from the CNS.     

Neurological findings in early treated phenylketonuria

Twenty early treated, normal intelligent patients (IQ: mean 101.4, SD 10.0; age: mean 10.11, SD 1.3 years) with classical phenylketonuria and 20 age-, sex- and IQ-matched healthy controls were investigated for neurological outcome, especially with regard to fine motor ability using the motor performance task ("Motorische Leistungsserie"). No pathological findings were seen on clinical neurological examination. The patient group had significantly poorer results in a concentration task (Test-d-2) as well as in some subtests of the motor performance task. Patients had difficulties in tasks which needed speed and precision of arm-hand-finger movements. High serum phenylalanine concentrations were significantly correlated with these deficiencies in fine motor ability. Our data demonstrated mild neurological impairment even in early and relatively strictly treated patients with phenylketonuria.