Iridium catalysts with bicyclic pyridine-phosphinite ligands: asymmetric hydrogenation of olefins and furan derivatives.
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Biomedical subjects
Publications and source records attributed to Stefan Kaiser.
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BACKGROUND: The Stroop interference test requires executive control functions, in particular inhibition of a learned routine (in this case word reading). Depressive patients show deficits on tests of executive function. However, the impact of confounding variables like type of depression and anxiety level is not yet elucidated for depressive patients. This is of clinical importance, since executive functions seem to play an important role in predicting treatment response and functional outcome. METHODS: 23 depressive patients and 27 healthy subjects performed a computerized mixed trial Stroop task. Depressive patients were divided according to DSM-IV diagnosis into melancholic and non-melancholic subgroups. Furthermore the level of anxiety was assessed in all subjects. RESULTS: When depressed patients were analyzed as a whole group, they showed only a trend towards higher Stroop interference effect at the beginning of the task. When analysis was performed using according to DSM-IV defined melancholic and non-melancholic subgroups, only non-melancholic patients were impaired in the Stroop task compared to melancholic patients and healthy subjects. LIMITATIONS: The sample size was small resulting in low statistical power. Furthermore, the patients were medicated. CONCLUSIONS: The unexpected result that melancholic patients perform better than non-melancholic ones may be due to their more pronounced rigidity, which makes them more resistant against distraction. Hence, more detailed psychopathological assessment is desirable for future investigations in executive functions of melancholic patients.
Eight genotypes (A-H) of hepatitis B virus (HBV) have been identified. However, the impact of different genotypes on the clinical course of hepatitis B infection remains controversial. We investigated the frequency and clinical outcome of HBV genotypes and genotype mixtures in HBV-infected patients from Vietnam, Europe, and Africa. In addition, we analyzed the effects of genotype mixtures on alterations in in vitro viral replication. In Asian patients, seven genotypes (A-G) were detected, with A, C, and D predominating. In European and African patients, only genotypes A, C, D, and G were identified. Genotype mixtures were more frequently encountered in African than in Asian (P = .01) and European patients (P = .06). In Asian patients, the predominant genotype mixtures included A/C and C/D, compared to C/D in European and A/D in African patients. Genotype A was more frequent in asymptomatic compared with symptomatic patients (P < .0001). Genotype C was more frequent in patients with hepatocellular carcinoma (HCC; P = .02). Genotype mixtures were more frequently encountered in patients with chronic hepatitis in comparison to patients with acute hepatitis B (P = .015), liver cirrhosis (P = .013), and HCC (P = .002). Viral loads in patients infected with genotype mixtures were significantly higher in comparison to patients with a single genotype (P = .019). Genotype mixtures were also associated with increased in vitro HBV replication. In conclusion, infection with mixtures of HBV genotypes is frequent in Asia, Africa, and Europe. Differences in the replication-phenotype of single genotypes compared to genotype-mixtures suggest that co-infection with different HBV-genotypes is associated with altered pathogenesis and clinical outcome.
Asymmetric hydrogenation of olefins is one of the most useful reactions for the synthesis of optically active compounds, especially in industry. However, the application range of the catalysts developed so far is limited to alkenes with a coordinating functional group or an aryl substituent next to the double bond. We have found a class of chiral iridium catalysts that give high enantioselectivity in the hydrogenation of unfunctionalized, trialkyl-substituted olefins. Because these catalysts do not require the presence of any particular functional group or aryl substituent in the substrate, they considerably broaden the scope of asymmetric hydrogenation.
The aim of this study was to investigate the event-related potential correlates of response inhibition in the N2 time window, specifically in the auditory modality. A paired tone Go/Nogo paradigm elicited an enhanced fronto-central negativity in the Nogo condition, which was accompanied by a concurring inferior fronto-temporal positivity. In contrast to most previous studies our data provide evidence for a fronto-central Nogo-N2 component in the auditory modality.
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The Stroop test requires executive control functions, in particular inhibition of a learned routine (in this case, word reading). The spatiotemporal analysis of brain activation during Stroop task execution was performed in 16 healthy subjects using high-density event-related potentials (ERPs) and dipole source modeling (BESA software). Scalp ERP analysis revealed the neurophysiological substrate of the interference effect: first, a greater negativity in the incongruent as compared to the congruent and neutral conditions was found between 350 and 450 ms poststimulus over left frontocentral scalp regions. Source analysis of the difference wave (incongruent-congruent) indicated that a generator localized in left prefrontal cortex (PFC) contributed to this effect. Second, immediately after the first effect, a greater positivity in the incongruent as compared to the congruent and neutral conditions developed between 450 and 550 ms poststimulus over midline frontocentral scalp regions. A generator of this effect was located in right anterior cingulate cortex (ACC). ACC activation seems to follow the activation of PFC with some overlap between the two components. Possible interpretation of this finding is that PFC signals ACC when executive control is required and ACC implements the control.
Hematopoietic stem cells (HSCs), with their dual ability for self-renewal and multilineage differentiation, constitute an essential component of hematopoietic transplantations. Human fetal liver (FL) represents a promising alternative HSC source, and we previously reported simple culture conditions allowing long-term expansion of FL hematopoietic progenitors. In the present study, we used the nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mouse xenotransplantation assay to confirm that human FL is rich in NOD/SCID-repopulating cells (SRCs) and to show that these culture conditions repeatedly maintained short- and long-term SRCs from various FL samples for at least 28 days. Quantitative limited dilution analysis in NOD/SCID mice demonstrated for the first time that a 10- to over a 100-fold net expansion of FL SRCs could be achieved after 28 days of culture. The efficiency of this culture system may lead to an increase in the use of FL as a source of HSCs for transplantation in adult patients, as previously demonstrated with umbilical cord blood under different culture conditions.
Growing evidence suggests an impairment of executive control functions in depression. The aim of this study was to investigate whether depressive patients show a specific impairment of executive control in a response inhibition task and to investigate its neurophysiological correlates using event-related potentials. We analyzed data from 16 patients with unipolar depression and 16 healthy controls using an auditory Go/Nogo task. High resolution event-related potentials (ERPs) were recorded. Depressive patients performed similar to controls in the Go task, but worse in the Nogo task, which required response inhibition. ERPs revealed the neurophysiological correlate of this deficit. Both groups showed the same voltage pattern in the Go task. However, in the Nogo task depressive patients showed a reduction of an early fronto-temporal positivity in the N2 time window, which was associated with response inhibition in healthy subjects. This effect could not be explained by increased task difficulty in the Nogo task. There was no difference between groups in later stages of processing as indexed by the P3 complex. Therefore, the findings suggest a specific deficit in response inhibition, which requires executive control. This deficit is thought to reflect dysfunctional activation of the network subserving executive control during an early stage of cortical processing.
A new procedure to model extended cortical sources from EEG and MEG recordings based on a probabilistic approach is presented. The method (SPMECS) was implemented within the framework of maximum likelihood estimators. Neuronal activity generating EEG or MEG signals was characterized by the number of sources and their location and extension. Based on the noise distribution of the measured data, source configurations were associated with the according value of the likelihood function. To find the most likely source, i.e., the maximum likelihood estimator, and its level of confidence, a stochastic solver (Metropolis algorithm) was applied. The method presented supports the incorporation of virtually any constraint, e.g., based on physiological and anatomical a priori knowledge. Thus, ambiguity of the ill-posed inverse problem was reduced considerably by confining sources to the cortical surface extracted from individual MR images. The influence of different levels and types of noise on the outcome was investigated by means of simulations. Somatosensory evoked magnetic fields analyzed by the method presented suggest that larger extended cortical areas are involved in the processing of combined finger stimulation as compared to single finger stimulation.
We conducted a prospective, long-term audit of lamotrigine and topiramate as add-on treatment for refractory epilepsy. A total of 55 patients participated in the study. Five years after starting the drug 7/20 patients remained on lamotrigine and 13/35 on topiramate. The patients still on the study drugs showed an improvement in seizure frequency, with 5/7 patients being seizure free on lamotrigine and 4/13 on topiramate. Furthermore, we assessed quality of life using the quality of life assessment schedule and found a significant improvement for the patients still on the study drugs. These data suggest that about one third of the patients on lamotrigine or topiramate as add-on therapy stay on the drug in the long term. These patients are likely to benefit with respect to objective and subjective outcome measures.