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Showing papers by "University of Tübingen published in 1996"


Journal ArticleDOI
Claude Amsler1, Michael Doser2, Mario Antonelli, D. M. Asner3  +173 moreInstitutions (86)
TL;DR: This biennial Review summarizes much of particle physics, using data from previous editions.

12,798 citations


Journal ArticleDOI
TL;DR: The effectiveness and validity of 11 important mood induction procedures (MIPs) were comparatively evaluated by meta-analytical procedures as discussed by the authors, and two hundred and fifty effects of the experimental induction of positive, elated and negative, depressed mood in adult, non-clinical samples were integrated.
Abstract: The effectiveness and validity of 11 important mood induction procedures (MIPs) were comparatively evaluated by meta-analytical procedures. Two hundred and fifty effects of the experimental induction of positive, elated and negative, depressed mood in adult, non-clinical samples were integrated. Effect sizes were generally larger for negative than for positive mood inductions. The presentation of a film or story turned out to be most effective in inducing both positive and negative mood states. The effects are especially large when subjects are explicitly instructed to enter the specified mood state. For elated mood, all other MIPs yielded considerably lower effectiveness scores. For the induction of negative mood states, Imagination, Velten, Music, Social Interaction and Feedback MIPs were about as effective as the Film/Story MIP without instruction. Induction effects covaried with several study characteristics. Effects tend to be smaller when demand characteristics are controlled or subjects are not informed about the purpose of the experiment. For behavioural measures, effects are smaller than for self-reports but still larger than zero. Hence, the effects of MIPs can be partly, but not fully due to demand effects.

1,059 citations


Journal ArticleDOI
08 Aug 1996-Nature
TL;DR: It is reported that the responses of direction-selective neurons in monkey visual cortex are greatly influenced by attention, and that this modulation occurs as early in the cortical hierarchy as the level of the middle temporal visual area (MT).
Abstract: THE visual system is constantly inundated with information received by the eyes, only a fraction of which seems to reach visual awareness. This selection process is one of the functions ascribed to visual attention1–6. Although many studies have investigated the role of attention in shaping neuronal representations in the visual cortex, few have focused on attentional modulation of neuronal signals related to visual motion. Here we report that the responses of direction-selective neurons in monkey visual cortex are greatly influenced by attention, and that this modulation occurs as early in the cortical hierarchy as the level of the middle temporal visual area (MT). Our finding demonstrates a stronger and earlier influence of attention on motion processing along the dorsal visual pathway than previously recognized.

1,022 citations


Journal ArticleDOI
TL;DR: The nucleotide sequence of icaABC suggests that the three genes are organized in an operon and that they are co‐transcribed from the mapped ica A promoter, suggesting that Ica A has N‐acetylglucosaminyltransferase activity in the formation of PIA.
Abstract: The Staphylococcus epidermidis genes icaABC are involved in the synthesis of the polysaccharide intercellular adhesin (PIA), which is located mainly on the cell surface, as shown by immunofluorescence studies with PIA-specific antiserum. PIA was shown to be a linear beta-1,6-linked glucosaminoglycan composed of at least 130 2-deoxy-2-amino-D-glucopyranosyl residues of which 80-85% are N-acetylated, the rest being non-N-acetylated and positively charged. A transposon insertion in the icaABC gene cluster (ica, intercellular adhesion) led to the loss of several traits, such as the ability to form a biofilm on a polystyrene surface, cell aggregation, and PIA production. The mutant could be complemented by transformation with the icaABC-carrying plasmid pCN27. Transfer of pCN27 into the heterologous host Staphylococcus carnosus led to the formation of large cell aggregates, the formation of a biofilm on a glass surface, and PIA expression. The nucleotide sequence of icaABC suggests that the three genes are organized in an operon and that they are co-transcribed from the mapped icaA promoter. IcaA contains four potential transmembrane helices, indicative of a membrane location. The deduced IcaA sequence shows similarity to those of polysaccharide-polymerizing enzymes, the most pronounced being with a Rhizobium meliloti N-acetylglucosaminyltransferase involved in lipo-chitin biosynthesis (22.5% overall identity and 37.4% overall similarity). This similarity suggests that IcaA has N-acetylglucosaminyltransferase activity in the formation of the beta-1, 6-linked N-acetyl-D-glucosaminyl polymer. IcaB is secreted into the medium and contains a typical signal peptide. IcaC is hydrophobic and contains six predicted transmembrane helices distributed over its entire length, typical for an integral membrane protein. Neither IcaB nor IcaC shares similarity with known proteins, and their function is unknown. Inactivation of icaA, icaB, or icaC in pCN27 led to the complete loss of the intercellular adhesion phenotype in S. carnosus, suggesting that all three genes are involved in intercellular adhesion, PIA expression, and translocation.

931 citations


Journal ArticleDOI
TL;DR: In this paper, the Mg concentrations within single chambers of the planktic foraminifer Globigerinoides sacculifer (BRADY) maintained under controlled laboratory conditions were measured at variable temperatures (19.5-29.5 °C) and constant salinity and (2) at variable salinity (22-45

808 citations


Journal ArticleDOI
TL;DR: Deterministic parsers specified by finite state cascades may be more accurate than exhaustive search stochastic context free parsers and extended at modest cost to construct parse trees with finite feature structures.
Abstract: Finite state cascades represent an attractive architecture for parsing unrestricted text. Deterministic parsers specified by finite state cascades are fast and reliable. They can be extended at modest cost to construct parse trees with finite feature structures. Finally, such deterministic parsers do not necessarily involve trading off accuracy against speed — they may in fact be more accurate than exhaustive search stochastic context free parsers.

558 citations


Journal ArticleDOI
TL;DR: In this paper, the structural properties, thermal expansion, electrical conductivity, thermodynamic stability, and surface properties of bismuth oxide and solid solutions with face centred cubic, rhombohedral, tetragonal or layer structures are reviewed.

554 citations


Journal ArticleDOI
TL;DR: The results suggest that STM functions by preventing incorporation of cells in the meristem center into differentiating organ primordia and that this role can completely account for all defects observed in stm mutants.
Abstract: The function of the SHOOT MERISTEMLESS (STM) gene in shoot and floral meristems throughout Arabidopsis development has been analyzed. The results show that STM plays a major role in maintaining shoot and floral meristems. In an allelic series of stm mutants the shoot meristem was either reduced or completely absent in mature embryos and mutant seedling cotyledons showed partial fusion, indicating that the STM gene affects embryonic shoot meristem development and spacing of cotyledons. Postembryonically, stm mutants initiated adventitious shoot development at a position corresponding to the shoot meristem in wild-type. Repetitively initiated defective mutant shoot and floral meristems were consumed during primordia formation and typically terminated prematurely in fused ectopic primordia, indicating that STM is required for continuous shoot and floral meristem function. Analogous defects were observed in stm embryonic and postembryonic development suggesting that similar mechanisms are employed in embryonic and postembryonic organ primordia initiation. Allelic combination suggest different thresholds for STM requirement during plant development. STM requirement could not be bypassed by standard growth factor regimes or by shoot regeneration from calli. The results suggest that STM functions by preventing incorporation of cells in the meristem center into differentiating organ primordia and that this role can completely account for all defects observed in stm mutants. Mutations in the WUSCHEL (WUS) and ZWILLE (ZLL) genes result in defective organization and premature termination of shoot meristems. Genetic interactions between STM, WUS and ZLL were analyzed and the results indicate that STM acts upstream of WUS and ZLL. Therefore, while STM appears to function in keeping central meristem cells undifferentiated, WUS and ZLL seem to be subsequently required for proper function of these cells.

470 citations


Journal ArticleDOI
TL;DR: This article found that the belief in a just world (BJW) is related to psychological well-being, and suggested that studies exploring this relationship might benefit by making the distinction between the BJW for self versus for others or in general.
Abstract: Studies have shown that the belief in a just world (BJW) is related to psychological well-being. The authors suggest that studies exploring this relationship might benefit by making the distinction between the BJW for self versus for others or in general. In two studies, the authors assessed subjects' perceptions of depression, stress, and life satisfaction for self and for others. Subjects also completed measures of the five-factor model of personality. As predicted, the BJW for self most strongly and consistently predicted decreases in depression and stress, and increases in life satisfaction. When the five personality dimensions were included in the analyses, the BJW for self and for others continued to predict life satisfaction but not depression and stress. The implications of these results concerning the relationship between the BJW and psychological well-being, and how the just world is conceptualized, are discussed.

447 citations


Journal ArticleDOI
20 Dec 1996-Science
TL;DR: Results indicate that cGKII plays a central role in diverse physiological processes and develops dwarfism that was caused by a severe defect in endochondral ossification at the growth plates.
Abstract: Cyclic guanosine 3',5'-monophosphate (cGMP)-dependent protein kinases (cGKs) mediate cellular signaling induced by nitric oxide and cGMP. Mice deficient in the type II cGK were resistant to Escherichia coli STa, an enterotoxin that stimulates cGMP accumulation and intestinal fluid secretion. The cGKII-deficient mice also developed dwarfism that was caused by a severe defect in endochondral ossification at the growth plates. These results indicate that cGKII plays a central role in diverse physiological processes.

403 citations


Journal Article
TL;DR: In six patients with increasing human thyroglobulin levels, it was found that 18FDG whole-body PET localized positive neck metastases of papillary thyroid carcinomas that were histologically confirmed after extirpation.
Abstract: We conducted a prospective study to define the sensitivity of 131I scintigraphy and 18FDG PET whole-body scanning in the detection of thyroid cancer and metastases. Methods: Forty-one patients with differentiated thyroid carcinoma who underwent thyroidectomy and 131I elimination of the remaining thyroid were studied by 18FDG whole-body PET in 52 examinations and by 131I whole-body scanning. Results: Combined 18FDG and 131I imaging resulted in a sensitivity of about 95%, with alternating uptake of 131I and 18FDG in the metastases: 131I trapping metastases with no 18FDG uptake and 18FDG trapping metastases with no 131I uptake. Five uptake types were differentiated. Alternating uptake was found in about 90% of the patients, which was nearly identical to the sensitivity of the combined 131I/18FDG investigation. In six patients with increasing human thyroglobulin levels, we found that 18FDG whole-body PET localized positive neck metastases of papillary thyroid carcinomas that were histologically confirmed after extirpation. Conclusion: Combination 18FDG and 131I whole-body imaging protocol enables detection of local recurrence or metastases on whole-body scans that are often not shown by other imaging methods. Biochemical grading of thyroid cancer may also be possible with this method: Tumors with remaining functional differentiation for hormone synthesis and iodine uptake have low glucose metabolism in more than 95%; tumors without this functional differentiation of 131I uptake show high glucose metabolism. Fluorine-18-FDG uptake seems to be an indicator of poor functional differentiation, and possibly higher malignancy, in thyroid cancer.

Journal ArticleDOI
TL;DR: The isolation and characterization of transposon (Tn917) mutants of Staphylococcus epidermidis O-47 which were biofilm negative in the polystyrene microtiter plate assay are described and a 60-kDa protein is postulated to function as the adhesin for binding to plastic.
Abstract: Biofilm formation is thought to result from the concerted action of primary attachment to a specific surface and accumulation in multilayered cell clusters Here we describe the isolation and characterization of transposon (Tn917) mutants of Staphylococcus epidermidis O-47 which were biofilm negative in the polystyrene microtiter plate assay Among 5,000 Tn917 insertion mutants, 4 biofilm-negative mutants were isolated Each mutant carried one copy of Tn917 The mutants were divided into two phenotypic classes: class A (mut1 and mut1a) and class B (mut2 and mut2a) Mutants of phenotypic class A lacked four cell surface proteins, were less hydrophobic, and were affected in primary attachment to polystyrene, but were still able to form multilayered cell clusters They were able to form a biofilm on a glass surface, a trait that was even more pronounced than in the wild-type stain O-47 Loss of several surface proteins might have led to the reduced surface hydrophilic structures, thus favoring primary attachment to a glass surface and leading to subsequent biofilm formation Mutants of phenotype class B were able to attach to polystyrene but were unable to form multilayered cell clusters, had unchanged cell surface proteins and hydrophobicity, and were unable to form a biofilm on a glass surface, mut1 and mut2 could be complemented by wild-type DNA fragments containing the Tn917 insertion sites of mut1 and mut2, respectively The complemented biofilm-positive clone mut1 (pRC20) produced a 60-kDa protein which is postulated to function as the adhesin for binding to plastic The traits of binding to polystyrene and the ability to form multilayered cell clusters are phenotypically and genetically distinct

Journal ArticleDOI
TL;DR: It is shown that new mRNA and protein synthesis, activation of ICE-like proteases, and ROS production are sequential events in K+ deprivation-induced apoptosis of cerebellar granule neurons.
Abstract: Potassium (K+) deprivation-induced apoptosis of cerebellar granule neurons requires new mRNA and protein synthesis. Using a fluorogenic substrate for interleukin-1beta converting enzyme (ICE), we show that K+ deprivation of cerebellar granule neurons induces cycloheximide-sensitive ICE-like protease activity. A peptide inhibitor of ICE-like protease activity, Ac-YVAD-chloromethylketone (Ac-YVAD-CMK), prevents K+ deprivation-induced apoptosis. Further, reactive oxygen species (ROS) are essential mediators of K+ deprivation-induced apoptosis of cerebellar granule neurons because neuronal death is also blocked by superoxide dismutase, N-acetyl-L-cysteine, and free radical spin traps. Using fluorescent assays, we show that ROS production after K+ deprivation is blocked by actinomycin D, cycloheximide, and Ac-YVAD-CMK, suggesting that ROS act downstream of gene transcription, mRNA translation, and ICE activation. Taken together, we show that new mRNA and protein synthesis, activation of ICE-like proteases, and ROS production are sequential events in K+ deprivation-induced apoptosis of cerebellar granule neurons.

Journal ArticleDOI
01 Jun 1996-Geology
TL;DR: In this article, the authors examined mid-Cretaceous radiolarian faunas, carbonate isotopic and organic matter type data of Deep Sea Drilling Project and Ocean Drilling Program cores from the North Atlantic, and samples from outcrops of the western Tethys from central and northern Italy.
Abstract: The relation between sea-level changes, plankton productivity, and evolution, as well as the occurrence of anoxic sediments, provides an interesting avenue of paleooceanographic research. In this context, we examined mid-Cretaceous radiolarian faunas, carbonate isotopic and organic matter type data of Deep Sea Drilling Project and Ocean Drilling Program cores from the North Atlantic, and samples from outcrops of the western Tethys from central and northern Italy. Former studies indicate that an expansion of the oxygen minimum zone caused plankton extinctions at the Cenomanian-Turonian boundary. An expanded oxygen minimum zone would destroy deeper habitats of planktic foraminifera, causing the extinction of deeper dwelling forms. Although this model is well established for the Cenomanian-Turonian boundary, not much is known about the causes of extinctions and radiations during the entire mid-Cretaceous (Aptian-Turonian). We demonstrate that the dimension of the oxygen minimum zone, which depends on the relative sea level and the corresponding nutrient supply, causes the complex pattern of evolution and radiation of planktic protozoa and the sedimentation of black shales in the mid-Cretaceous. This new depositional model allows correlation of micropaleontologic data and different types of black shales in the pelagic realm within a sequence stratigraphic framework.

Journal ArticleDOI
TL;DR: In this paper, the full trajectories of particles and not just the final positions of each particle are computed using a C++ class library, which can be easily extended to simulate the effects of manufacturing processes or interacting bodies.
Abstract: Animating the drape of different cloths must address complex physical behaviors. This particle approach uses optimizations that make it faster than earlier implementations and allow it to simulate behavior over time. The modeling system presented computes the full trajectories of particles and not just the final positions. This offers several important advantages. Since the full history of each particle is known, hysteresis effects can be modeled accurately. The Kawabata (1980) experimental data for different textiles can be input directly to the model. The effects of external forces, especially those produced by wind or moving solid bodies, can be modeled accurately. Despite this extra dimension of detail, our system computes final positions considerably faster than the times given by Breen, House and Wozny (1994). Our model can be easily extended to simulate the effects of manufacturing processes or interacting bodies. In particular, high stresses of the kind that occur in manufacturing can only be modeled if the full trajectory of each particle is known. We have implemented our model as a C++ class library. Particle systems are more flexible than approaches using continuum mechanics. Our system's fast computation times, mainly due to the numerical solution of ordinary differential equations, compare favorably to approaches using a finite-element method. Therefore, our approach might be an interesting alternative for other engineering problems currently solved by a finite-element method, for example, the computation of minimal surfaces, heavy membranes, vibrating membranes and population dynamics.

Book ChapterDOI
01 Jan 1996
TL;DR: For example, this article found that ecomorphologically similar species may be clearly differentiated by behavioral traits such as spatial segregation in habitat use, roost site selection, foraging strategies, and diet.
Abstract: The study of processes that influence the distribution, diversity, and abundance of species is one of the most challenging and complex fields in biology. Many basic questions are still controversial. As the results of an increasing number of studies clearly demonstrate, good data on temporal and spatial variability in community composition and species abundance are essential for formulating and evaluating hypotheses about the processes determining organization of communities and diversity of species. However, recent studies indicate that ecomorphologically similar species may be clearly differentiated by behavioral traits such as spatial segregation in habitat use, roost site selection, foraging strategies, and diet. Ecomorphological predictions alone would have placed these species closer together in the community than they actually are. Furthermore, relative abundance of well-sampled species showed individual year-to-year variation. Some frugivorous species with large seasonal variation in numbers may be migratory, but except for one species that declined, long-term population trends remained rather constant. Long-term monitoring of bats at many localities is urgently needed to build databases for intercommunity comparisons.

Journal ArticleDOI
TL;DR: The green luminescence of polycrystalline ZnO is investigated by diffuse reflection, steady state and time-resolved photoluminescence as well as photoconductivity and is assigned to a donor-acceptor-type transition.

Journal ArticleDOI
TL;DR: The historical development of Ro is reviewed, an exposition of the recently formalised theory to define and calculate R0 for structured populations is given, and the interaction of demography and epidemiology is returned to for an example of the use of the concept to study vaccination campaigns.
Abstract: In epidemiology R0 denotes the average number of secondary cases of an infectious disease that one case would generate in a completely susceptible population. This concept is among the foremost and most valuable ideas that mathematical thinking has brought to epidemic theory. In this contribution, we first review the historical development of Ro, from demography to epidemiology, proceed to give an exposition of the recently formalised theory to define and calculate R0 for structured populations, return to the interaction of demography and epidemiology for an example of the use of the concept to study vaccination campaigns and finally we deal with statistical aspects of estimating R0. In the appendix we discuss some issues of current attention.


Journal ArticleDOI
TL;DR: In this paper, the Minimal Quantified Structure Constraint (MQSC) constraint is introduced to prevent the in situ element of the scope-marking construction from moving at LF to either a position reserved for wh-phrases, or even higher up in the structure.
Abstract: In this paper I argue for a restriction on certain types of LF movement, which I call ‘wh-related LF movement’. Evidence comes from a number of wh-in-situ constructions in German, such as the scope-marking construction and multiple questions. For semantic reasons, the in situ element in those constructions has to move at LF to either a position reserved for wh-phrases, or even higher up in the structure. The restriction (the Minimal Quantified Structure Constraint, MQSC) is that an intervening quantified expression blocks this movement. In the case of every, the MQSC leads to an unambiguously distributive interpretation of the question. In the case of all other intervening operators, including negation, it leads to ungrammaticality.

Journal ArticleDOI
TL;DR: Results suggest that blockade of HERG channels by terfenadine and astemizole might contribute to the cardiac side effects of these compounds.

Journal ArticleDOI
01 Oct 1996-Brain
TL;DR: The principal finding of this study is that mutations of the SCA2 and SCA3 gene cause phenotypes which can be distinguished in vivo by recording of eye movements and morphometric MRI analysis.
Abstract: Sixty-five patients suffering from autosomal dominant cerebellar ataxia-I(ADCA-1) were subjected genotype phenotype correlation analysis using molecular genetic assignment to the spinocerebellar ataxia type 1, 2 or 3 (SCA1, -2 or -3) locus, clinical examination, eye movement recording and morphometric analysis of MRIs. Pyramidal tract signs, pale discs and dysphagia were more frequent in SCA1 compared SCA2 and SCA3 patients. Saccade velocity was reduced in 56% of SCA1 and all SCA2, but only in 30% of SCA3 patients. MRIs of SCA2 patients showed atrophy changes typical of severe olivopontocerebellar atrophy (OPCA). The morphological changes in SCA1 were similar but less pronounced. In contrast, SCA3 patients had only mild cerebellar and brain stem atrophy distinct from typical OPCA. The principal finding of this study is that mutations of the SCA2 and SCA3 gene cause phenotypes which can be distinguished in vivo by recording of eye movements and morphometric MRI analysis. Correlative plotting of saccade velocity and diameter of the middle cerebellar peduncle yields a clear separation of SCA2 and SCA3. Spinocerebellar ataxia type I falls into an intermediate range that overlaps with both SCA2 and SCA3. However, the clinical syndrome observed in SCA1 patients is different from that in SCA2 and SCA3.

Journal ArticleDOI
TL;DR: In combination with the contractile force of outer hair cells, it is proposed that inertial motion of the tectorial membrane provides the necessary conditions to allow positive feedback of mechanical energy into the cochlear partition, thereby amplifying and tuning the co chlear response.
Abstract: The tectorial membrane has long been postulated as playing a role in the exquisite sensitivity of the cochlea. In particular, it has been proposed that the tectorial membrane provides a second resonant system, in addition to that of the basilar membrane, which contributes to the amplification of the motion of the cochlear partition. Until now, technical difficulties had prevented vibration measurements of the tectorial membrane and, therefore, precluded direct evidence of a mechanical resonance. In the study reported here, the vibration of the tectorial membrane was measured in two orthogonal directions by using a novel method of combining laser interferometry with a photodiode technique. It is shown experimentally that the motion of the tectorial membrane is resonant at a frequency of 0.5 octave (oct) below the resonant frequency of the basilar membrane and polarized parallel to the reticular lamina. It is concluded that the resonant motion of the tectorial membrane is due to a parallel resonance between the mass of the tectorial membrane and the compliance of the stereocilia of the outer hair cells. Moreover, in combination with the contractile force of outer hair cells, it is proposed that inertial motion of the tectorial membrane provides the necessary conditions to allow positive feedback of mechanical energy into the cochlear partition, thereby amplifying and tuning the cochlear response.

Journal ArticleDOI
TL;DR: The applications of separation techniques using ultra-filtration in connection with functional soluble polymers for the removal of environmentally relevant and toxic substances from waters are reviewed in this article, where several factors influencing the separation of the target substances such as membrane type, solution composition, synergism, polymer adsorption, deformation of macromolecules, and hydrodynamics are evaluated.
Abstract: The applications of separation techniques using ultrafiltration in connection with functional soluble polymers for the removal of environmentally relevant and toxic substances from waters are reviewed. The types of interactions of the soluble polymers with low molecular mass compounds, the criteria for selecting the appropriate polymeric agents, and the binding conditions are discussed. Several factors influencing the separation of the target substances such as membrane type, solution composition, synergism, polymer adsorption, deformation of macromolecules, and hydrodynamics are evaluated and highlighted. Chemical, electrochemical, and thermal regeneration aspects are also covered. Finally, an overview on varius preparative and analytical application examples is presented.

Proceedings ArticleDOI
27 Oct 1996
TL;DR: This work presents a new algorithm to reduce the number of triangles of a mesh without exceeding a user defined Hausdorff distance between the original and simplified mesh, which allows one to generate a hierarchical geometric representation in a canonical way and automatically preserves sharp edges.
Abstract: In many cases the surfaces of geometric models consist of a large number of triangles. Several algorithms were developed to reduce the number of triangles required to approximate such objects. Algorithms that measure the deviation between the approximated object and the original object are only available for special cases. We use the Hausdorff distance between the original and the simplified mesh as a geometrically meaningful error value which can be applied to arbitrary triangle meshes. We present a new algorithm to reduce the number of triangles of a mesh without exceeding a user defined Hausdorff distance between the original and simplified mesh. As this distance is parameterization independent, its use as error measure is superior to the use of the L/sup /spl infin//-Norm between parameterized surfaces. Furthermore the Hausdorff distance is always less than the distance induced by the L/sup /spl infin//-Norm. This results in higher reduction rates. Excellent results were achieved by the new decimation algorithm for triangle meshes that has been used in different application areas such as volume rendering, terrain modeling and the approximations of parameterized surfaces. The key advantages of the new algorithm are: it guarantees a user defined position dependent approximation error; it allows one to generate a hierarchical geometric representation in a canonical way; it automatically preserves sharp edges.

Journal ArticleDOI
TL;DR: The data suggest that TNF-alpha and high glucose modulate insulin receptor-signaling through different mechanisms: (a) T NF-alpha modulates insulin receptor signals by PTPase activation, whereas glucose acts through activation of PKC.
Abstract: Inhibition of insulin receptor signaling by high glucose levels and by TNF-alpha was recently observed in different cell systems. The aim of the present study was to characterize the mechanism of TNF-alpha-induced insulin receptor inhibition and to compare the consequences of TNF-alpha- and hyperglycemia-induced insulin receptor inhibition for signal transduction downstream from the IR. TNF-alpha (0.5-10 nM) and high glucose (25 mM) showed similar rapid kinetics of inhibition (5-10 min, > 50%) of insulin receptor autophosphorylation in NIH3T3 cells overexpressing the human insulin receptor. TNF-alpha effects were completely prevented by the phosphotyrosine phosphatase (PTPase) inhibitors orthovanadate (40 microM) and phenylarsenoxide (35 microM), but they were unaffected by the protein kinase C (PKC) inhibitor H7 (0.1 mM), the phosphatidylinositol-3 kinase inhibitor wortmannin (5 microM), and the thiazolidindione troglitazone (CS045) (2 microgram/ml). In contrast, glucose effects were prevented by PKC inhibitors and CS045 but unaffected by PTPase inhibitors and wortmannin. To assess effects on downstream signaling, tyrosine phosphorylation of the following substrate proteins of the insulin receptor was determined: insulin receptor substrate-1, the coupling protein Shc, focal adhesion kinase (FAK125), and unidentified proteins of 130 kD, 60 kD. Hyperglycemia (25 mM glucose) and TNF-alpha showed analogous (> 50% inhibition) effects on tyrosine phosphorylation of insulin receptor substrate-1, Shc, p60, and p44, whereas opposite effects were observed for tyrosine phosphorylation of FAK125, which is dephosphorylated after insulin stimulation. Whereas TNF-alpha did not prevent insulin-induced dephosphorylation of FAK125, 25 mM glucose blocked this insulin effect completely. In summary, the data suggest that TNF-alpha and high glucose modulate insulin receptor-signaling through different mechanisms: (a) TNF-alpha modulates insulin receptor signals by PTPase activation, whereas glucose acts through activation of PKC. (b) Differences in modulation of the insulin receptor signaling cascade are found with TNF-alpha and high glucose: Hyperglycemia-induced insulin receptor inhibition blocks both insulin receptor-dependent tyrosine phosphorylation and dephosphorylation of insulin receptor substrate proteins. In contrast, TNF-alpha blocks only substrate phosphorylation, and it does not block insulin-induced substrate dephosphorylation. The different effects on FAK125 regulation allow the speculation that long-term cell effects related to FAK125 activity might develop in a different way in hyperglycemia- and TNF-alpha-dependent insulin resistance.

Journal ArticleDOI
TL;DR: The proposed discretization uses convolution quadrature based on the first- and second-order backward difference methods in time, and piecewise linear finite elements in space to study the numerical approximation of an integro-differential equation.
Abstract: We study the numerical approximation of an integro-differential equation which is intermediate between the heat and wave equations. The proposed discretization uses convolution quadrature based on the first- and second-order backward difference methods in time, and piecewise linear finite elements in space. Optimal-order error bounds in terms of the initial data and the inhomogeneity are shown for positive times, without assumptions of spatial regularity of the data.

Journal ArticleDOI
TL;DR: In this article, a total of 61 sites (more than 700 cores) have been sampled mainly from limestones (Zongshan Formation, Jidula Formation Member II, Zongpu Formation), sandstones (Jidula Group Member III) and graywackes (Gamba Group Member II), with ages well defined from detailed lithological and biostratigraphic analyses.

Journal ArticleDOI
01 Jun 1996-Brain
TL;DR: Measurement of the speed and axis of eye rotation during spontaneous nystagmus and the three-dimensional properties of the vestibuloocular reflex suggest that vestibular neuritis is a partial and not a complete unilateral Vestibular lesion and that this partial lesion affects the superior division of thevestibular nerve which includes the afferents from the horizontal and anterior SCCs.
Abstract: Acute unilateral vestibulopathy, or vestibular neuritis, is the second most common cause of vertigo. To quantify the involvement of the different semicircular canal (SCC) afferents in this disease, we studied the three-dimensional (3D) properties of the vestibuloocular reflex (VOR) in 16 patients 3-10 days after onset of symptoms. Using 3D magnetic search coil eye movement recordings, we measured the speed and axis of eye rotation during spontaneous nystagmus and during rotation in the planes of the different SCCs. In all patients, spontaneous nystagmus axes clustered between the direction expected with involvement of just one horizontal SCC and the direction expected with combined involvement of the horizontal and anterior SCC on one side. Likewise, dynamic asymmetries were found only during rotations about axes which stimulated the ipsilesional horizontal or ipsilesional anterior SCCs. No asymmetry was found when the ipsilesional posterior SCC was stimulated. Thus, both measurements suggest that vestibular neuritis is a partial and not a complete unilateral vestibular lesion and that this partial lesion affects the superior division of the vestibular nerve which includes the afferents from the horizontal and anterior SCCs.

Journal ArticleDOI
TL;DR: The presence of enzymatic activity of nitric oxide synthase in fungi and a higher plant and an effect of Nitric oxide in fungal photophysiology are reported for the first time.
Abstract: Indications for the occurrence of nitric oxide synthases in Dictyostelium, Neurospora, Phycomyces and the leguminous plant Mucuna hassjoo as well as a physiological role of nitric oxide in Neurospora crassa are demonstrated. An exogenous nitic oxide donor, sodium nitroprusside, inhibited light-stimulated conidiation in N. crassa. Specific inhibitors of nitric oxide synthase, like the arginine derivatives NG -nitro-L-arginine (L-NA) and NG-nitro-L-arginine-methyl ester (L-NAME), enhanced conidiation in darkness nad in the light, whereas the stereoisomer D-NAME was inactive. This communication reports to our knowledge the first time the presence of enzymatic activity of nitric oxide synthase in fungi and a higher plant and an effect of nitric oxide in fungal photo-physiology.