Showing papers by "Saarland University published in 1999"
TL;DR: Conditional mutagenesis of Gr in the nervous system provides genetic evidence for the importance of Gr signalling in emotional behaviour because mutant animals show an impaired behavioural response to stress and display reduced anxiety.
Abstract: The glucocorticoid receptor (Gr, encoded by the gene Grl1) controls transcription of target genes both directly by interaction with DNA regulatory elements and indirectly by cross-talk with other transcription factors. In response to various stimuli, including stress, glucocorticoids coordinate metabolic, endocrine, immune and nervous system responses and ensure an adequate profile of transcription. In the brain, Gr has been proposed to modulate emotional behaviour, cognitive functions and addictive states. Previously, these aspects were not studied in the absence of functional Gr because inactivation of Grl1 in mice causes lethality at birth (F.T., C.K. and G.S., unpublished data). Therefore, we generated tissue-specific mutations of this gene using the Cre/loxP -recombination system. This allowed us to generate viable adult mice with loss of Gr function in selected tissues. Loss of Gr function in the nervous system impairs hypothalamus-pituitary-adrenal (HPA)-axis regulation, resulting in increased glucocorticoid (GC) levels that lead to symptoms reminiscent of those observed in Cushing syndrome. Conditional mutagenesis of Gr in the nervous system provides genetic evidence for the importance of Gr signalling in emotional behaviour because mutant animals show an impaired behavioural response to stress and display reduced anxiety.
1,754 citations
TL;DR: It is demonstrated that pocket profiles are nearly independent of the remaining HLA-DR cleft, and this approach has implications for the development of epitope-based vaccines.
Abstract: Generation of tissue-specific and promiscuous HLA ligand databases using
DNA microarrays and virtual HLA class II matrices
805 citations
TL;DR: An astonishingly high rate of rotator cuff tears in patients with asymptomatic shoulders was demonstrated with increasing patient age and must to a certain extent be regarded as "normal" degenerative attrition, not necessarily causing pain and functional impairment.
775 citations
TL;DR: The results demonstrate a very rapid excitatory action of neurotrophins, placing them among the most potent endogenous neuro-excitants in the mammalian central nervous system described so far.
Abstract: Neurotrophins are a family of structurally related proteins that regulate the survival, differentiation and maintenance of function of different populations of peripheral and central neurons. They are also essential for modulating activity-dependent neuronal plasticity. Here we show that neurotrophins elicit action potentials in central neurons. Even at low concentrations, brain-derived neurotrophic factor (BDNF) excited neurons in the hippocampus, cortex and cerebellum. We found that BDNF and neurotrophin-4/5 depolarized neurons just as rapidly as the neurotransmitter glutamate, even at a more than thousand-fold lower concentration. Neurotrophin-3 produced much smaller responses, and nerve growth factor was ineffective. The neurotrophin-induced depolarization resulted from the activation of a sodium ion conductance which was reversibly blocked by K-252a, a protein kinase blocker which prefers tyrosine kinase Trk receptors. Our results demonstrate a very rapid excitatory action of neurotrophins, placing them among the most potent endogenous neuro-excitants in the mammalian central nervous system described so far.
544 citations
TL;DR: In this paper, the authors deal with doping titania by Cr 3+ and Mo 5+ ions and show the complex interactions between variations in lifetime of charge carriers, adsorption properties and photocatalytic behaviour.
Abstract: Titanium dioxide is one of the most efficient photocatalysts for the detoxification of organically charged waste water. However, this material suffers from the drawback of poor absorption properties because of a band gap of 3.2 eV. Thus, wavelengths shorter than 400 nm are needed for light induced generation of electron–hole pairs. Therefore, doping with transition metal ions is interesting for inducing a batho-chromic shift of the band gap. However, this doping changes other physical properties such as lifetime of electron–hole pairs and adsorption characteristics. This paper deals with doping titania by Cr 3+ and Mo 5+ ions. We want to show the complex interactions between variations in lifetime of charge carriers, adsorption properties and photocatalytic behaviour.
437 citations
TL;DR: The data suggest that beginning cannabis use during early adolescence may lead to enduring effects on specific attentional functions in adulthood, as apparently, vulnerable periods during brain development exist that are subject to persistent alterations by interfering exogenous cannabinoids.
Abstract: Rationale and objective: The present study tested the hypothesis that chronic interference by cann- abis with endogenous cannabinoid systems during peri- pubertal development causes specific and persistent brain alterations in humans. As an index of cannabi- noid action, visual scanning, along with other atten- tional functions, was chosen. Visual scanning undergoes a major maturation process around age 12-15 years and, in addition, the visual system is known to react specifically and sensitively to cannabinoids. Methods: From 250 individuals consuming cannabis regularly, 99 healthy pure cannabis users were selected. They were free of any other past or present drug abuse, or history of neuropsychiatric disease. After an interview, physi- cal examination, analysis of routine laboratory para- meters, plasma/urine analyses for drugs, and MMPI testing, users and respective controls were subjected to a computer-assisted attention test battery comprising visual scanning, alertness, divided attention, flexibility, and working memory. Results : Of the potential pre- dictors of test performance within the user group, including present age, age of onset of cannabis use, degree of acute intoxication (THC+THCOH plasma levels), and cumulative toxicity (estimated total life dose), an early age of onset turned out to be the only predictor, predicting impaired reaction times exclu- sively in visual scanning. Early-onset users (onset before age 16; n = 48) showed a significant impairment in reaction times in this function, whereas late-onset users (onset after age 16; n = 51) did not di⁄er from controls (n = 49). Conclusions: These data suggest that beginning cannabis use during early adolescence may lead to enduring e⁄ects on specific attentional func- tions in adulthood. Apparently, vulnerable periods dur- ing brain development exist that are subject to persistent alterations by interfering exogenous cannabi- noids.
383 citations
TL;DR: In this retrospective analysis, the information provided by FDG-PET would have contributed to a substantial reduction of the size of radiotherapy portals, particularly for patients with tumor-associated dys- or atelectasis.
Abstract: Purpose: 18 F-deoxyglucose positron emission tomography (FDG-PET) is increasingly applied in the staging of lung cancer (LC). This study analyzes the potential contribution of PET in radiotherapy planning for LC with special respect to tumor-associated atelectasis. Methods and Materials: Thirty-four patients with histologically confirmed LC, who had been examined by PET during pretreatment staging, were included. All were irradiated after CT-based therapy planning with anterior/posterior (AP) portals encompassing the primary tumor and the mediastinum (CT portals, CP). The result of the PET examination was unknown in treatment planning. In retrospect, a PET portal (PP) was delineated and compared with the CP. Results: In 12/34 cases, the shape and/or size of the portals were changed, primarily ( n = 10) the size of the fields was reduced. The median area of CP was 182 cm 2 versus 167 cm 2 of PP. Seventeen of 34 patients had dys- or atelectasis caused by a central primary tumor. In these cases, differences between CP and PP were significantly more frequent than in the other patients (8/17 vs. 3/17, p = 0.03). Conclusion: In this retrospective analysis, the information provided by FDG-PET would have contributed to a substantial reduction of the size of radiotherapy portals. This applies particuarly for patients with tumor-associated dys- or atelectasis.
347 citations
TL;DR: In this article, the authors modified the Burke equation to take into account a linear dependence of grain-boundary pinning on grain size, and the form of the resulting grain growth curve is surprisingly similar to Burke's solution; in fact, a constant rescaling of the boundary mobility parameter is sufficient to map one solution approximately onto the other.
264 citations
TL;DR: For interprocedural analysis, existing methods are examined and a new approach that is especially tailored for the cache analysis is presented, which allows for a static classification of the cache behavior of memory references of programs.
Abstract: interpretation is a technique for the static detection of dynamic properties of programs. It is semantics based, that is, it computes approximative properties of the semantics of programs. On this basis, it supports correctness proofs of analyses. It replaces commonly used ad hoc techniques by systematic, provable ones, and it allows for the automatic generation of analyzers from specifications by existing tools. In this work, abstract interpretation is applied to the problem of predicting the cache behavior of programs. semantics of machine programs are defined which determine the contents of caches. For interprocedural analysis, existing methods are examined and a new approach that is especially tailored for the cache analysis is presented. This allows for a static classification of the cache behavior of memory references of programs. The calculated information can be used to improve worst case execution time estimations. It is possible to analyze instruction, data, and combined instruction/data caches for common (re)placement and write strategies. Experimental results are presented that demonstrate the applicability of the analyses.
230 citations
TL;DR: It is shown that micromolar concentrations of Cd can increase ROS production and exert a toxic effect on PT cells andhibitors of the proteasome such as MG‐132 or lactacystin, as well as lysosomo‐tropic weak bases such as chloroquine or NH4Cl, significantly reduced the decrease of Na+/K+‐ATPase α1‐subunit induced by Cd, and in combination abolished the effect of C d on Na
Abstract: The mechanisms of cadmium (Cd)-dependent nephrotoxicity were studied in a rat proximal tubule (PT) cell line. CdCl(2) (5 microM) increased the production of reactive oxygen species (ROS), as determined by oxidation of dihydrorhodamine 123 to fluorescent rhodamine 123. The levels of ubiquitin-conjugated cellular proteins were increased by Cd in a time-dependent fashion (maximum at 24-48 h). This was prevented by coincubation with the thiol antioxidant N-acetylcysteine (NAC, 15 mM). Cd also increased apoptosis (controls: 2.4+/-1.6%; Cd: 8.1+/-1.9%), but not necrosis (controls: 0.5 +/- 0.3%; Cd: 1.4+/- 2.5%). Exposure of PT cells with Cd decreased protein levels of the catalytic subunit (alpha1) of Na+/K(+)-ATPase, a long-lived membrane protein (t(1/2)>48 h) that drives reabsorption of ions and nutrients through Na(+)-dependent transporters in PT. Incubation of PT cells for 48 h with Cd decreased Na+/K(+)-ATPase alpha1-subunit, as determined by immunoblotting, by approximately 50%, and NAC largely prevented this effect. Inhibitors of the proteasome such as MG-132 (20 microM) or lactacystin (10 microM), as well as lysosomotropic weak bases such as chloroquine (0.2 mM) or NH(4)Cl (30 mM), significantly reduced the decrease of Na(+)/K(+)-ATPase alpha1-subunit induced by Cd, and in combination abolished the effect of Cd on Na+/K(+)-ATPase. Immunofluorescence labeling of Na+/K(+)-ATPase showed a reduced expression of the protein in the plasma membrane of Cd-exposed cells. After addition of lactacystin and chloroquine to Cd-exposed PT cells, immunoreactive material accumulated into intracellular vesicles. The data indicate that micromolar concentrations of Cd can increase ROS production and exert a toxic effect on PT cells. Oxidative damage increases the degradation of Na+/K(+)-ATPase through both the proteasomal and endo-/lysosomal proteolytic pathways. Degradation of oxidatively damaged Na+/K(+)-ATPase may contribute to the 'Fanconi syndrome'-like Na(+)-dependent transport defects associated with Cd-nephrotoxicity.
228 citations
TL;DR: It is indicated that the treatment of intrabony defects with enamel matrix proteins or with bioabsorbable membranes enhances the formation of a new connective tissue attachment in humans.
Abstract: The aim of the present study was to evaluate histologically in humans the healing of advanced intrabony defects following treatment with enamel matrix proteins (EMD) or guided tissue regeneration (GTR). Fourteen patients, each of them displaying 1 advanced intrabony defect around teeth scheduled for extraction were included in the study. The defects were treated randomly either with an enamel matrix protein derivative (Emdogain, BIORA AB, Malmo, Sweden) or with a bioabsorbable membrane (Resolut, Regenerative Material, W.L. Gore & Assoc., Flagstaff, Arizona, USA). At baseline the mean probing pocket depth (PPD) in the EMD group was 11.3 +/- 1.8 mm and the mean clinical attachment level (CAL) 12.1 +/- 2.0 mm, whereas in the GTR group the mean PPD was 11.4 +/- 2.2 mm and the mean CAL 13.3 +/- 2.3 mm. Healing was uneventful in all cases. Neither allergic reactions against EMD or the bioabsorbable membrane, nor suppuration or abscesses were observed. The clinical results revealed at 6 months in the EMD group a mean PPD of 5.6 +/- 1.3 mm and a mean CAL of 9.1 +/- 1.5 mm. In the GTR group the mean PPD was 5.6 +/- 1.3 mm and the mean CAL 10.1 +/- 1.5 mm. The histological analysis showed in the EMD group a mean 2.6 +/- 1.0 mm of new attachment (i.e. new cementum with inserting collagen fibers) and a mean 0.9 +/- 1.0 mm of new bone. In this group, the formation of new attachment was not always followed by bone regeneration. In the GTR group, the mean new attachment was 2.4 +/- 1.0 mm and the mean new bone 2.1 +/- 1.0 mm. In every case treated with GTR, the formation of new attachment was followed by a varying amount of new bone. After both types of regenerative treatment the newly formed cementum displayed a predominantly cellular character. The findings of the present study indicate that the treatment of intrabony defects with enamel matrix proteins or with bioabsorbable membranes enhances the formation of a new connective tissue attachment in humans.
TL;DR: Abstract interpretation is applied to the problem of predicting the cache behavior of programs and a new approach that is especially tailored for the cache analysis is presented, allowing for a static classification of the Cache behavior of memory references of programs.
TL;DR: A weak partial metric on the poset of formal balls of a metric space can be used to construct the completion of classical metric spaces from the domain-theoretic rounded ideal completion.
Abstract: Partial metrics are generalised metrics with non-zero self-distances. We slightly generalise Matthews' original definition of partial metrics, yielding a notion of weak partial metric. After considering weak partial metric spaces in general, we introduce a weak partial metric on the poset of formal balls of a metric space. This weak partial metric can be used to construct the completion of classical metric spaces from the domain-theoretic rounded ideal completion.
TL;DR: In this paper, the photoemission core-level spectra are analyzed in terms of a simple cluster model leading to estimates for the charge-transfer energy, the Coulomb correlation energy, and the hybridization strength V. This trend is attributed mostly to the increasing number of empty d states in the early transition metals which enhances the effective metal-ligand hybridization.
Abstract: We have performed photoemission and inverse photoemission experiments on a series of 3d-transition-metal oxides with formal ionic configuration from to . The photoemission core-level spectra are analysed in terms of a simple cluster model leading to estimates for the charge-transfer energy , the Coulomb correlation energy , and the hybridization strength V. It is found that the ratio of the correlation energy to the hybridization energy significantly decreases from the late to the early transition metal oxides. This trend is attributed mostly to the increasing number of empty d states in the early transition metals which enhances the effective metal-ligand hybridization. We also compare the experimental valence band spectra with densities of states (DOS) from band-structure calculations. The rather good agreement between the theoretical DOS and the measured single-particle excitation spectra of the early 3d-transition-metal oxides as opposed to the failure of the one-electron description for most of the late transition metal oxides supports the results of the cluster model analysis.
TL;DR: It is indicated that functional KATP channels are present in principal neurones, interneurones and glial cells of the rat hippocampus, but at highly different densities in the four cell types studied.
Abstract: 1. The distribution of ATP-sensitive K+ channels (KATP channels) was investigated in four cell types in hippocampal slices prepared from 10- to 13-day-old rats: CA1 pyramidal cells, interneurones of stratum radiatum in CA1, complex glial cells of the same area and granule cells of the dentate gyrus. The neuronal cell types were identified visually and characterized by the shapes and patterns of their action potentials and by neurobiotin labelling. 2. The patch-clamp technique was used to study the sensitivity of whole-cell currents to diazoxide (0.3 mM), a KATP channel opener, and to tolbutamide (0.5 mM) or glibenclamide (20 microM), two KATP channel inhibitors. The fraction of cells in which whole-cell currents were activated by diazoxide and inhibited by tolbutamide was 26% of pyramidal cells, 89 % of interneurones, 100% of glial cells and 89% of granule cells. The reversal potential of the diazoxide-induced current was at the K+ equilibrium potential and a similar current activated spontaneously when cells were dialysed with an ATP-free pipette solution. 3. Using the single-cell RT-PCR method, the presence of mRNA encoding KATP channel subunits (Kir6.1, Kir6.2, SUR1 and SUR2) was examined in CA1 pyramidal cells and interneurones. Subunit mRNA combinations that can result in functional KATP channels (Kir6.1 together with SUR1, Kir6.2 together with SUR1 or SUR2) were detected in only 17% of the pyramidal cells. On the other hand, KATP channels may be formed in 75% of the interneurones, mainly by the combination of Kir6.2 with SUR1 (58% of all interneurones). 4. The results of these combined analyses indicate that functional KATP channels are present in principal neurones, interneurones and glial cells of the rat hippocampus, but at highly different densities in the four cell types studied.
TL;DR: The aim of the present work was to investigate the preparation of nanoparticles (NP) as potential drug carriers for proteins and the hydrophilic protein bovine serum albumin (BSA) was chosen as the model drug to be incorporated within NP.
TL;DR: The freeze-thawing procedure significantly affects chromatin structure and sperm morphology, especially in the head and the tail regions, and this may explain the lower fertilization rate and IVF/ICSI outcome when frozen-thawed spermatozoa are used.
Abstract: Cryopreservation is known to impair sperm motility and decrease the fertilization rate by detrimental effects on acrosomal structure and acrosin activity. However, the consequences of cryopreservation on the integrity of the sperm nucleus, chromatin stability and centrosome are less clear. The present study was designed to determine the effect of the freeze-thawing procedure on chromatin condensation (aniline blue staining) and the morphology (strict criteria) and membrane integrity of human spermatozoa. The structural and functional characteristics of the sperm plasma membrane were measured by the eosin-test and hypo-osmotic swelling test which were done separately. Sperm cryopreservation was performed on semen samples from two groups of men classified as fertile (n = 20) and subfertile (n = 72), based on their reproductive history and semen analysis according to WHO guidelines. The mean percentage of condensed chromatin, morphologically normal spermatozoa and membrane integrity in all semen samples investigated (n = 92) decreased significantly (p = 0.0001) after freeze-thawing, in comparison to the value observed prior to freezing. By comparing the semen samples between fertile and subfertile patients, significantly (p = 0.0009) greater damage was demonstrated in the subfertile than in the fertile group. Furthermore, no significant difference was observed between the two groups with regard to the morphological alteration and structural as well as functional damage of the sperm membrane. In conclusion, the freeze-thawing procedure significantly affects chromatin structure and sperm morphology, especially in the head and the tail regions, and this may explain the lower fertilization rate and IVF/ICSI outcome when frozen-thawed spermatozoa are used. In addition, this study demonstrates that chromatin condensation is a sensitive parameter for the evaluation of cryodamage of semen samples from fertile and subfertile patients, though subfertile patients with very poor semen characteristics have yet to be studied. It is therefore recommended that chromatin condensation be used as an additional parameter for the assessment of sperm quality after freeze-thawing.
TL;DR: A primary cell culture model of human alveolar epithelial cells has been established, which appears to be a valuable in vitro model for pulmonary drug delivery and transport studies.
Abstract: Purpose To develop a cell culture model of human alveolar epithelial cells in primary culture for the in vitro study of pulmonary absorption and transport
TL;DR: A retrospective analysis of prognostic factors for survival and time to non-CNS death in 528 patients treated at a single institution with radiotherapy or surgery plus radiotherapy for brain metastases essentially confirmed the value of RPA-derived prognostic classes, as published by the RTOG.
Abstract: Purpose: To determine whether or not Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) derived prognostic classes for patients with brain metastases are generally applicable and can be recommended as rational strategy for patient selection for future clinical trials. Inclusion of time to non-CNS death as additional endpoint besides death from any cause might result in further valuable information, as survival limitation due to uncontrolled extracranial disease can be explored. Methods: We performed a retrospective analysis of prognostic factors for survival and time to non-CNS death in 528 patients treated at a single institution with radiotherapy or surgery plus radiotherapy for brain metastases. For this purpose, patients were divided into groups with Karnofsky performance status (KPS) Results: Median overall survival was 2.9 months (2.0 months for patients with KPS p p p > 0.05 for RPA class II versus III). However, it was 8.5 months in RPA class II patients with controlled primary tumor, which was found to be the only prognostic factor for time to non-CNS death in patients with KPS ≥70%. In patients with KPS Conclusions: Despite some differences, this analysis essentially confirmed the value of RPA-derived prognostic classes, as published by the RTOG, when survival was chosen as endpoint. RPA class I patients seem to be most likely to profit from aggressive treatment strategies and should be included in appropriate clinical trials. However, their number appears to be very limited. Considering time to non-CNS death, our results suggest that certain patients in RPA class II also might benefit from increased local control of brain metastases.
TL;DR: It is concluded that hTRP3 forms non‐selective plasmalemmal cation channels that function as a pathway for agonist‐induced Ca2+ influx.
Abstract: 1. We combined patch clamp and fura-2 fluorescence methods to characterize human TRP3 (hTRP3) channels heterologously expressed in cultured bovine pulmonary artery endothelial (CPAE) cells, which do not express the bovine trp3 isoform (btrp3) but express btrp1 and btrp4. 2. ATP, bradykinin and intracellular InsP3 activated a non-selective cation current (IhTRP3) in htrp3-transfected CPAE cells but not in non-transfected wild-type cells. During agonist stimulation, the sustained rise in [Ca2+]i was significantly higher in htrp3-transfected cells than in control CPAE cells. 3. The permeability for monovalent cations was PNa > PCs approximately PK >> PNMDG and the ratio PCa/PNa was 1.62 +/- 0.27 (n = 11). Removal of extracellular Ca2+ enhanced the amplitude of the agonist-activated IhTRP3 as well as that of the basal current The trivalent cations La3+ and Gd3+ were potent blockers of IhTRP3 (the IC50 for La3+ was 24.4 +/- 0.7 microM). 4. The single-channel conductance of the channels activated by ATP, assessed by noise analysis, was 23 pS. 5. Thapsigargin and 2,5-di-tert-butyl-1, 4-benzohydroquinone (BHQ), inhibitors of the organellar Ca2+-ATPase, failed to activate IhTRP3. U-73122, a phospholipase C blocker, inhibited IhTRP3 that had been activated by ATP and bradykinin. Thimerosal, an InsP3 receptor-sensitizing compound, enhanced IhTRP3, but calmidazolium, a calmodulin antagonist, did not affect IhTRP3. 6. It is concluded that hTRP3 forms non-selective plasmalemmal cation channels that function as a pathway for agonist-induced Ca2+ influx.
TL;DR: Tanetin, previously thought to be a new structure, is now formulated as the known 6-hydroxykaempferol 3,6,4'-trimethyl ether, based on NMR measurements.
TL;DR: The results demonstrate that the novel antiangiogenic concept of targeting the tyrosine kinase of Flk-1/KDR by means of a small molecule inhibitor represents an efficient strategy to control growth and progression of angiogenesis-dependent tumors.
20 Sep 1999
TL;DR: A general expressivity result is proved showing that even the weak form of binding offered by the ↓ operator easily leads to undecidability in hybrid languages in which it is possible to bind nominals.
Abstract: Hybrid languages are extended modal languages which can refer to (or even quantify over) states. Such languages are better behaved proof theoretically than ordinary modal languages for they internalize the apparatus of labeled deduction. Moreover, they arise naturally in a variety of applications, including description logic and temporal reasoning. Thus it would be useful to have a map of their complexity-theoretic properties, and this paper provides one.
Our work falls into two parts. We first examine the basic hybrid language and its multi-modal and tense logical cousins. We show that the basic hybrid language (and indeed, multi-modal hybrid languages) are no more complex than ordinary uni-modal logic: all have PSPACE-complete K-satisfiability problems. We then show that adding even one nominal to tense logic raises complexity from pspace to EXPTIME. In the second part we turn to stronger hybrid languages in which it is possible to bind nominals. We prove a general expressivity result showing that even the weak form of binding offered by the ↓ operator easily leads to undecidability.
TL;DR: In this paper, the authors proposed a non-cooperative game-theoretic approach to evaluate the distribution of power between decision-making bodies in the European Union, based on the distance between a player's ideal point and the equilibrium outcome of a game.
Abstract: In this paper we propose a new method to evaluate the distribution of power between decision-making bodies in the European Union. Conventional methods that measure the voting power of players, such as the Banzhaf, Johnston, Holler and Shapley-Shubik indices, are insufficient for this purpose. They take no account, in an endogenous way, of the differences in the abilities of players to affect the outcome of decision-making, which are a result of the existence of political institutions. We propose a different way to measure decision-making power based on the distance between a player's ideal point and the equilibrium outcome of a game. While all previous indices are based on cooperative game theory, the index developed in this paper is based on non-cooperative game theory, which has been the dominant thrust of theoretical politics and economics in the last years. The new index is applied to legislative procedures in the European Union.
TL;DR: In this article, the authors considered Newton-type methods for the stable solution of nonlinear ill-posed problems and verified the regularization property of these methods, that is, the iterates converge to a solution of the nonlinear problem with exact data when the noise level tends to zero.
Abstract: Inexact Newton methods for the stable solution of nonlinear ill-posed problems are considered. The corresponding inner scheme can be chosen to be any linear regularization with a sufficient modulus of convergence. The regularization property of these Newton-type algorithms is verified, that is, the iterates converge to a solution of the nonlinear problem with exact data when the noise level tends to zero. Moreover, convergence rates are given. Finally, implementation issues are discussed and the algorithm is applied to a parameter identification problem for an elliptic PDE. The numerical results reproduce nicely theoretical predictions and show the efficiency of the proposed method.
TL;DR: Mucosal SIV replication and intestinal CD4(+) T cell depletion are early events in SIV-infected rhesus macaques, and the structural changes of the mucosa strongly support the concept of HIV/SIV-induced enteropathy.
TL;DR: Efficient treatment of phenylketonuria has to go beyond recommendations for blood Phe level control and must include adequate dietary training, medical as well as psychological counselling of the patient and his family, and a protocol for monitoring outcome.
Abstract: Treatment of hyperphenylalaninaemias due to phenylalanine hydroxylase deficiency with a low phenylalanine (Phe) diet is highly successful in preventing neurological impairment and mental retardation There is consensus that, for an optimal outcome, treatment should start as early as possible, and that strict blood Phe level control is of primary importance during the first years of life, but for adolescent and adult patients international treatment recommendations show a great variability A working party of the German Working Group for Metabolic Diseases has evaluated research results on IQ data, speech development, behavioural problems, educational progress, neuropsychological results, electroencephalography, magnetic resonance imaging, and clinical neurology Based on the actual knowledge, recommendations were formulated with regard to indication of treatment, differential diagnosis, and Phe level control during different age periods The development of the early-and-strictly-treated patient in middle and late adulthood still remains to be investigated Therefore, the recommendations should be regarded as provisional and subject to future research Efficient treatment of phenylketonuria has to go beyond recommendations for blood Phe level control and must include adequate dietary training, medical as well as psychological counselling of the patient and his family, and a protocol for monitoring outcome
TL;DR: It is found that back-propagating action potentials (APs) evoked Na+ transients throughout the proximal part of the dendritic tree and adjacent spines, the first demonstration of activity-induced Na+ accumulation in spines.
Abstract: Dendritic spines are assumed to be the smallest units of neuronal integration. Because of their miniature size, however, many of their functional properties are still unclear. New insights in spine physiology have been provided by two-photon laser-scanning microscopy which allows fluorescence imaging with high spatial resolution and minimal photodamage. For example, two-photon imaging has been employed successfully for the measurement of activity-induced calcium transients in individual spines. Here, we describe the first application of two-photon imaging to measure Na+ transients in spines and dendrites of CA1 pyramidal neurons in hippocampal slices. Whole-cell patch-clamped neurons were loaded with the Na+-indicator dye SBFI (sodium-binding benzofuran-isophthalate). In situ calibration of SBFI fluorescence with ionophores enabled the determination of the actual magnitude of the [Na+]i changes. We found that back-propagating action potentials (APs) evoked Na+ transients throughout the proximal part of the dendritic tree and adjacent spines. The action-potential-induced [Na+]i transients reached values of 4 mM for a train of 20 APs and monotonically decayed with a time constant of several seconds. These results represent the first demonstration of activity-induced Na+ accumulation in spines. Our results demonstrate that two-photon Na+ imaging represents a powerful tool for extending our knowledge on Na+ signaling in fine cellular subcompartments.
TL;DR: The correlation between the number of zinc ions bound to the Zn2+-beta-lactamase from Bacillus cereus and hydrolysis of benzylpenicillin and nitrocefin and a mutant where cysteine 168 is replaced by alanine is investigated.
TL;DR: An exceptionally stable 1:2 complex [FeL2]3− is formed from the ligand H3L and FeIII, which is a highly promising candidate for medical applications (e.g. for the treatment of iron overload).
Abstract: An exceptionally stable 1:2 complex [FeL2]3− is formed from the ligand H3L and FeIII. In contrast, the affinity of this ligand for other biometals is relatively small. These properties make H3L a highly promising candidate for medical applications (e.g. for the treatment of iron overload).