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Showing papers by "University of Freiburg published in 1993"


Book
01 Feb 1993
TL;DR: Inequalities for mixed volumes 7. Selected applications Appendix as discussed by the authors ] is a survey of mixed volumes with bounding boxes and quermass integrals, as well as a discussion of their applications.
Abstract: 1. Basic convexity 2. Boundary structure 3. Minkowski addition 4. Curvature measure and quermass integrals 5. Mixed volumes 6. Inequalities for mixed volumes 7. Selected applications Appendix.

3,954 citations


Journal ArticleDOI
15 Jul 1993-Nature
TL;DR: The observation that Raf-1 and PKCα cooperate in the transformation of NIH3T3 cells is consistent with such a direct interaction, and the Ser499 phosphorylation site is necessary for this synergism.
Abstract: The kinase Raf-1 can be activated by treatment of cells with mitogens and by the protein kinase C (PKC) activator 12-O-tetradecanoyl-phorbol-13-acetate (TPA) (reviewed in refs 1,2). Activated Raf-1 triggers a protein kinase cascade by direct phosphorylation of MAP kinase kinase, resulting in phosphorylation of ternary complex factor and Jun by MAP kinase. Here we investigate the molecular mechanism and biological consequences of PKC alpha-mediated Raf-1 activation in NIH3T3 fibroblasts. PKC alpha directly phosphorylates and activates Raf-1 both in vitro and in vivo. PKC alpha induces Raf-1 phosphorylation at several sites, including a serine residue at position 499. Mutation of serine at this position or at residue 259 does not abrogate Raf-1 stimulation by a combination of Ras plus the src tyrosine kinase Lck, but severely impedes Raf-1 activation by PKC alpha. Consistent with such a direct interaction is the observation that Raf-1 and PKC alpha cooperate in the transformation of NIH3T3 cells. The Ser499 phosphorylation site is necessary for this synergism.

1,245 citations


Journal ArticleDOI
TL;DR: In this article, the authors describe a system of rather different cellular components assembled to guarantee a specific and successful process of signal transduction between the signal and the gene, which are evolutionarily conserved and ubiquitously distributed amongst living organisms.
Abstract: The development and life-time of multicellular eukaryotic organisms represents a complex interplay of numerous proliferation and differentiation events that proceed in a highly ordered manner. As a prerequisite for those events, cells must respond to extracellular signals with a specific set of mechanisms that regulate or modulate gene expression. Between the signal and the gene, a system of rather different cellular components is assembled to guarantee a specific and successful process of signal transduction. Pathways of signal transduction, though differing remarkably in their complexity and in the use of cellular components, seem to obey certain principles which are evolutionarily conserved and ubiquitously distributed amongst living organisms. Extracellular signals, so-called ligands, either penetrate the cellular membrane or bind to the extracellular domain of receptors. Activated receptors as such, or in association with socalled transducers, are capable of activating effectors-either directly or by means of changing the amount or intracellular distribution of so-called second messengers. These second

1,229 citations


Journal Article
01 Feb 1993-Oncogene
TL;DR: The results obtained are in accordance with the view that the DNA damage-induced p53 accumulation may either inhibit cell growth, allowing DNA repair processes, or, in the case of severe damage, initiate apoptosis.
Abstract: Cancer therapy drugs, such as diamminedichloroplatinum (cisplatin), mitomycin C, etoposide and a number of other compounds, as well as energy-rich radiation, are known to act on cellular DNA. These agents are shown to induce nuclear accumulation of the so-called tumor-suppressor protein p53 in fibroblastoid cells, as well as in epithelioid normal and immortalized cells of murine, simian, and human origin. p53 accumulation starts a few hours after treatment and can remain detectable in surviving cells for at least 20 days. Accumulation occurs because of increased p53 protein stability and depends on ongoing translation. It is not the result of enhanced gene expression. A number of cell cycle inhibitors do not affect p53 protein accumulation, suggesting that the process may start from several points in the cell cycle. Since the increase in the nuclear p53 protein levels occurs within a few hours in most of the treated normal diploid cells, it is unlikely that the accumulated p53 protein is derived from a mutated p53 gene. The results obtained are in accordance with the view that the DNA damage-induced p53 accumulation may either inhibit cell growth, allowing DNA repair processes, or, in the case of severe damage, initiate apoptosis.

795 citations


Journal ArticleDOI
TL;DR: Hypercholesterolemia and advanced age selectively impair endothelium-mediated relaxation of the coronary microvasculature in response to acetylcholine, whereas endothelial dysfunction is restricted to epicardial arteries in age-matched normocholesterolemic patients with evidence of coronary atherosclerosis and/or hypertension.
Abstract: The effects of age, atherosclerosis, hypertension, and hypercholesterolemia on vascular function of the coronary circulation were studied by subselective intracoronary infusions of acetylcholine, which releases endothelium-derived relaxing factor, and papaverine, which directly relaxes vascular smooth muscle, in normal patients (n = 18; no risk factors for coronary artery disease), in patients with evidence of early atherosclerosis but normal cholesterol levels and normal blood pressure (n = 12), in patients with hypertension without left ventricular hypertrophy (n = 12), and in patients with hypercholesterolemia (n = 20). Papaverine-induced maximal increases in coronary blood flow were significantly greater in normals, but no differences were noted between the groups of patients with early atherosclerosis, with hypertension, and with hypercholesterolemia. The capacity of the coronary system to increase blood flow in response to acetylcholine was similar in normal and normocholesterolemic patients with epicardial atherosclerosis and/or hypertension but was significantly impaired in patients with hypercholesterolemia, irrespective of evidence of epicardial atherosclerotic lesions. Age (r = -0.62, P < 0.0001) and total serum cholesterol levels (r = -0.70; P < 0.0001) were the only significant independent predictors of a blunted coronary blood flow response to acetylcholine. Thus, hypercholesterolemia and advanced age selectively impair endothelium-mediated relaxation of the coronary microvasculature in response to acetylcholine, whereas endothelial dysfunction is restricted to epicardial arteries in age-matched normocholesterolemic patients with evidence of coronary atherosclerosis and/or hypertension.

692 citations


Journal ArticleDOI
TL;DR: It is hypothesize that an optomotor reflex is responsible for the occurrence of express saccades, one that is controlled by higher brain functions involved in disengaged visual attention and decision making and proposed a neural network as the basis for more elaborate mathematical models or computer simulations of the optom motor system in primates.
Abstract: One of the most intriguing and controversial observations in oculomotor research in recent years is the phenomenon of express saccades in monkeys and man. These are saccades with such short reaction times (100 msec in man, 70 msec in monkeys) that some experts on eye movements still regard them as artifacts or as anticipatory reactions that do not need any further explanation. On the other hand, some research groups consider them not only authentic but also a valuable means of investigating the mechanisms of saccade generation, the coordination of vision and eye movements, and the mechanisms of visual attention.This target article puts together pieces of experimental evidence in oculomotor and related research – with special emphasis on the express saccade – to enhance our present understanding of the coordination of vision, visual attention, and the eye movements subserving visual perception and cognition.We hypothesize that an optomotor reflex is responsible for the occurrence of express saccades, one that is controlled by higher brain functions involved in disengaged visual attention and decision making. We propose a neural network as the basis for more elaborate mathematical models or computer simulations of the optomotor system in primates.

602 citations


Journal ArticleDOI
TL;DR: All patients with pheochromocytomas should be screened for MEN-2 and von Hippel-Lindau disease to avert further morbidity and mortality in the patients and their families.
Abstract: Background Pheochromocytoma is a feature of two disorders with an autosomal dominant pattern of inheritance -- multiple endocrine neoplasia type 2 (MEN-2) (with medullary thyroid carcinoma and hyperparathyroidism) and von Hippel-Lindau disease (with angioma of the retina, hemangioblastoma of the central nervous system, renal-cell carcinoma, pancreatic cysts, and epididymal cystadenoma). The frequency of these syndromes in patients with pheochromocytoma is not known. Methods In an unselected group of patients with pheochromocytoma, we performed pentagastrin tests, parathyroid hormone assays, computed tomography (CT) or magnetic resonance imaging (MRI) of the brain, ophthalmoscopy, CT imaging of the abdomen, and ultrasonography of the testes. We also screened members of families with MEN-2 or von Hippel-Lindau disease for pheochromocytoma by measuring plasma and urine catecholamines and plasma chromogranin A and by performing abdominal ultrasonography, CT and MRI, and metaiodobenzylguanidine scintigraphy. R...

429 citations


Journal ArticleDOI
TL;DR: Endothelin 1, eicosanoids and sodium nitroprusside are able to modulate the contractility of stellate cells by inducing the disappearance of actin stress fibers in contracted cells.
Abstract: We have studied the contractility of liver sinusoidal stellate (Ito) cells stimulated with endothelin 1, nitric-oxide donors and eicosanoids. Contraction and relaxation of stellate cells were detected by the use of a silicone-rubber method that revealed the traction forces exerted by these cells. Endothelin 1 was a strong elicitor for stellate-cell contraction. 78, 55, 59 and 56% of stellate cells were contracted 2.5, 5, 10 and 20 min, respectively, after exposure to 10 nM endothelin 1. The effect of endothelin 1 was dose dependent and still detectable at an endothelin 1 concentration of 100 pM. Concomitantly, an endothelin-dependent formation of inositol phosphates was apparent; values of InsP, InsP2, and InsP3 were 881 +/- 99%, 1965 +/- 368%, and 791 +/- 120% of control, respectively, 20 min after addition of 10 nM endothelin 1. In addition, endothelin 1 caused a transient increase of [Ca2+]i in stellate cells from a basal value of 121 +/- 9 nM to maximal 1015 +/- 86 nM. These endothelin-1 effects were much stronger than those of the thromboxane-A2 analogue U46619 and of prostaglandin F2 alpha. In contrast, Iloprost, prostaglandin E2, and sodium nitroprusside promoted stellate-cell relaxation; for example, 82, 83 and 71% of stellate cells relaxed 5, 10, and 20 min, respectively, after addition of 500 microM sodium nitroprusside to contacted cells. Prostaglandin E2 and Iloprost led to elevation of cAMP levels in stellate cells from a basal value of 9.2 +/- 0.8 pmol/well to 55.1 +/- 8.0 and 122.2 +/- 12.2 pmol/well 10 min after addition of prostaglandin E2 (5 microM) and Iloprost (5 microM), respectively, in the presence of 3-isobutyl-1-methylxanthine (0.5 mM). However, sodium nitroprusside was a trigger for cGMP accumulation. Intracellular cGMP increased from a basal value of 0.9 +/- 0.07 pmol/well to 13.4 +/- 6.7 pmol/well 10 min after addition of 500 microM sodium nitroprusside into the medium. It is interesting that Iloprost and sodium nitroprusside also induced the disappearance of actin stress fibers in contracted cells; F-actin stress fibers became less numerous and de-aggregated; more than 90% of stellate cells were void of stress fibers after 10 microM Iloprost treatment for 30 min. Thus, endothelin 1, eicosanoids and sodium nitroprusside are able to modulate the contractility of stellate cells.(ABSTRACT TRUNCATED AT 400 WORDS)

386 citations


Journal ArticleDOI
TL;DR: In this paper, the authors proposed a nonlinear regularization method to calculate the relaxation spectrum in the terminal and plateau region of a polyamide polymer solution, which can be used to obtain a more complete relaxation spectrum.
Abstract: It is well known that the relaxation spectrum characterizing the linear viscoelastic properties of a polymer melt or solution is not directly accessible by an experiment. Therefore, it must be calculated from data for a material function. With Tikhonov regularization the relaxation spectrum in the terminal and plateau region can be calculated from data for a material function in the corresponding region. Serious difficulties arise however, if the spectrum should be determined in a larger range. These difficulties are caused by the considerably different contributions at short and long relaxation times. We show that these difficulties can be avoided by a nonlinear regularization method.

352 citations


Journal ArticleDOI
TL;DR: In this article, a two-step growth process based on the control of α permits the independent optimization of texture axis and surface morphology, offering the possibility to obtain smooth faceted diamond films for arbitrary film thickness.

315 citations


Journal ArticleDOI
TL;DR: The long-term administration of benzodiazepine hypnotics seems to be an inadequate treatment strategy in chronic insomnia, indicating that insomnia constitutes a significant burden for the primary care physicians.
Abstract: The aim of the study was to assess prevalence and treatment modalities of insomnia in general practice. To investigate the course of insomnia, a longitudinal study design was adopted. Two thousand five hundred and twelve patients (age 18–65 years) were investigated with a questionnaire in general practice (T1). Four months later (T2) and again 2 years later (T3) a questionnaire was sent to all patients who had complained about severe insomnia at the time of the first inquiry. To assess insomnia, operationalized diagnostic criteria were applied (DSM-III-R). Eighteen point seven percent suffered from severe, 12.2% suffered from moderate and 15% suffered from mild insomnia. In the course of 2 years insomnia appeared as a chronic health problem. A high comorbidity of severe insomnia was found with chronic somatic and psychiatric disorders, especially with depression. Of the severely insomniac patients, 23.9% used prescribed hypnotics habitually, mainly benzodiazepines. The use of prescribed hypnotics remained rather stable during the whole study period. More than half of the patients reported a daily use of the hypnotics for 1–5 years or longer, but only 22% of the severely insomniac patients reported at the time of the third inquiry a significant improvement of insomnia due to the administration of sleeping pills. Thus, the long-term administration of benzodiazepine hypnotics seems to be an inadequate treatment strategy in chronic insomnia. Whether the occurrence of rebound insomnia after benzodiazepine withdrawal may be one of the main factors for chronic hypnotic use requires discussion. Although insomnia may be an important symptom of many somatic and psychiatric disorders, the general practitioner was unaware in more than half of the cases that the patients suffered from a sleep problem. Severe insomniac patients displayed a higher mean number of medical consultations compared with good sleepers or patients with mild insomnia, indicating that insomnia constitutes a significant burden for the primary care physicians.

Journal ArticleDOI
TL;DR: The variations in metabolite concentrations, and especially the presence or absence of aliphatic signals, were proved to be indicators of the histologic grade of tumor.
Abstract: To better understand variations in spectra of brain tumors, 122 in vivo proton spectra of brain tumors in 82 patients were analyzed. The changes in relative metabolite concentrations compared with those in normal spectra and the presence of any new metabolite were assessed. To evaluate the clinical usefulness of in vivo hydrogen-1 magnetic resonance (MR) spectroscopy in brain tumors, the authors looked for specific spectral changes on the basis of tumor grade. All tumor spectra showed differences from normal reference spectra. The differential diagnosis of the spectra was limited because intraindividual differences between spectra of one tumor at different locations were often larger than differences between spectra of tumors with different histologic characteristics. However, the variations in metabolite concentrations, and especially the presence or absence of aliphatic signals, were proved to be indicators of the histologic grade of tumor. The observed spectral patterns conformed to a four-compartment ...

Journal ArticleDOI
Bernardo Adeva1, Shafqat Ahmad2, A. Arvidson3, B. Badelek4  +162 moreInstitutions (22)
TL;DR: In this paper, the spin-dependent structure function g1 p of the proton was measured in deep inelastic scattering of polarized muons off polarized protons, in the kinematic range 0.136±0.011 (stat.)± 0.011(syst.) at Q2 = 10GeV2.

Journal ArticleDOI
TL;DR: The occurrence of two molecular forms of this endothelial specific growth factor suggests different physiological roles of the two forms during placental development and differentiation.
Abstract: Placenta Growth Factor (PlGF) was recently discovered as a secreted growth factor for vascular endothelial cells and based on its homology to vascular endothelial growth factor (VEGF), can be classified as a new member of this growth factor family. We have carried out polymerase chain amplification (PCR) of RNA from human umbilical vein endothelial cells and placenta tissue and discovered a second species of PlGF, PlGF-2. PlGF-2 has a 21-amino acid insertion not present in PlGF-1 coding for a highly basic region near the C-terminus. This is similar to VEGF189. Northern analysis has shown, that the PlGF gene is expressed only in a limited number of cell types and tissues, e.g. human umbilical vein endothelial cells (HUVE) and placenta. Infection of Sf158 insect cells with recombinant baculoviruses specific for the two forms showed, that both, PlGF-1 and PlGF-2 are secreted efficiently into the supernatant and PlGF-2 can bind with high affinity to heparin. Both PlGF forms had a similar mitogenic potency for bovine aortic endothelial cells. Binding studies with 125I-VEGF165 demonstrate, that supernatant of PlGF expressing insect cells can compete for receptor binding. Similar to VEGF, PlGF can exist in different forms which are probably generated by differential splicing. The occurrence of two molecular forms of this endothelial specific growth factor suggests different physiological roles of the two forms during placental development and differentiation.

Journal ArticleDOI
TL;DR: This paper shows that the Glushkov automaton can be constructed in a time quadratic in the size of the expression, and that this is worst-case optimal, and shows that, modulo a technical condition, an expression is strongly unambiguous if and only if it is weakly unambiguous and in star-normal form.

Journal ArticleDOI
TL;DR: Resting RSA does not accurately predict individual differences in cardiac vagal tone, but RSA and heart period together do predict such individual differences reasonably well, and the relationship between individual variations in RSA and vagaltone is not improved by controlling respiratory parameters.
Abstract: Respiratory sinus arrhythmia (RSA) is frequently employed as an intra- and interindividual index of cardiac parasympathetic tone, although the relationship of RSA to interindividual differences in cardiac vagal tone remains questionable. Our study examined between- and within-subject relations among RSA, cardiac vagal tone, and respiratory parameters. Twenty-nine young adults performed two sessions of tasks under no medication and single and double autonomic blockade (intravenously administered propranolol and atropine). Parasympathetic tone was determined from heart period responses to complete vagal blockade. Results indicated the following. Resting RSA does not accurately predict individual differences in cardiac vagal tone. However, RSA and heart period together do predict such individual differences reasonably well. The relationship between individual variations in RSA and vagal tone is not improved by controlling respiratory parameters. Substantial cardiac vagal activity occurs during inspiration, and intraindividual variations in respiratory measures confound the association between RSA and cardiac vagal tone.

Journal ArticleDOI
TL;DR: The results suggest that, in the gap task, most of the naive subjects exhibit at least two clearly separated peaks in the distribution of the saccadic reaction times, which indicates that express saccades almost never overshoot.
Abstract: The saccadic eye movements of 20 naive adults, 7 naive teenagers, 12 naive children, and 4 trained adult subjects were measured using two single target saccade tasks; the gap and the overlap task. In the gap task, the fixation point was switched off before the target occurred; in the overlap task it remained on until the end of each trial. The target position was randomly selected 4° to the left or 4° to the right of the fixation point. The subjects were instructed to look at the target when it appeared, not to react as fast as possible. They were not given any feedback about their performance. The results suggest that, in the gap task, most of the naive subjects exhibit at least two (the teenagers certainly three) clearly separated peaks in the distribution of the saccadic reaction times. The first peak occurs between 100 and 135 ms (express saccades), the second one between 140 and 180 ms (fast regular), and a third peak may follow at about 200 ms (slow regular). Other subjects did not show clear signs of two modes in the range of 100 to 180 ms, and still others did not produce any reaction times below 135 ms. In the overlap task as well three or even more peaks were obtained at about the same positions along the reaction time scale of many, but not all subjects. Group data as well as those of individual subjects were fitted by the superposition of three gaussian functions. Segregating the reaction time data into saccades that over- or undershoot the target indicated that express saccades almost never overshoot. The results are discussed in relation to the different neural processes preceding the initiation of visually-guided saccades.

Journal ArticleDOI
TL;DR: The hypothesis that this new class of nitrogen fixation genes encodes components of an electron transfer system to nitrogenase was corroborated by analysing the effect of metronidazole.
Abstract: DNA sequence analysis of a 12236 bp fragment, which is located upstream of nifE in Rhodobacter capsulatus nif region A, revealed the presence of ten open reading frames With the exception of fdxC and fdxN, which encode a plant-type and a bacterial-type ferredoxin, the deduced products of these coding regions exhibited no significant homology to known proteins Analysis of defined insertion and deletion mutants demonstrated that six of these genes were required for nitrogen fixation Therefore, we propose to call these genes rnfA, rnfB, rnfC, rnfD, rnfE and rnfF (for Rhodobacter nitrogen fixation) Secondary structure predictions suggested that the rnf genes encode four potential membrane proteins and two putative iron-sulphur proteins, which contain cysteine motifs (C-X2-C-X2-C-X3-C-P) typical for [4Fe--4S] proteins Comparison of the in vivo and in vitro nitrogenase activities of fdxN and rnf mutants suggested that the products encoded by these genes are involved in electron transport to nitrogenase In addition, these mutants were shown to contain significantly reduced amounts of nitrogenase The hypothesis that this new class of nitrogen fixation genes encodes components of an electron transfer system to nitrogenase was corroborated by analysing the effect of metronidazole Both the fdxN and rnf mutants had higher growth yields in the presence of metronidazole than the wild type, suggesting that these mutants contained lower amounts of reduced ferredoxins

Journal ArticleDOI
TL;DR: The mechanisms of which nitric oxide and prostacyclin are released from endothelium-intact rabbit femoral arteries under resting conditions and after stimulation by either shear stress or acetylcholine were investigated.
Abstract: The mechanisms of which nitric oxide (NO) and prostacyclin (PGI2) are released from endothelium-intact rabbit femoral arteries under resting conditions and after stimulation by either shear stress or acetylcholine (ACh) were investigated. The concentration of NO in the effluate was determined by monitoring the NO-mediated stimulation of purified soluble guanylyl cyclase, and that of PGI2 was done using a specific radioimmunoassay for its stable hydrolysis product, 6-ketoprostaglandin F1 alpha, NO release under static (no-flow) conditions and in the absence of a stimulus accounted for 10-15% of the maximum release of NO from luminally perfused segments stimulated with ACh and was attenuated by removal of extracellular Ca2+. A six- to sevenfold increase in shear stress (from 0.15 to 1 dyn/cm2), generated either by vasoconstriction at constant flow or by an increase in flow at constant diameter, elicited a five- to sevenfold increase in NO release, which was correlated with increasing shear stress. The same increase in shear stress also enhanced the release of PGI2 from the femoral artery segments by 11- to 12-fold. Removal of extracellular Ca2+ abolished the shear stress-dependent PGI2 released but did not affect that of NO. In contrast, the ACh-stimulated NO release was strongly inhibited in the absence of extracellular Ca2+ (78% inhibition). Charybdotoxin, an inhibitor of Ca(2+)-activated K+ channels, and glibenclamide, an inhibitor of the ATP-sensitive K+ channel, had no effect on the shear stress-dependent release of NO.(ABSTRACT TRUNCATED AT 250 WORDS)

Journal Article
TL;DR: A procedure for RNA extraction from different types of FFPE tissues, involving digestion with proteinase K followed by guanidinium-thiocyanate acid phenol extraction and DNase I digestion, finding the universally expressed porphobilinogen deaminase mRNA proved to be useful as a positive control because of the lack of pseudogenes.
Abstract: Specific amplification of nucleic acid sequences by PCR has been extensively used for the detection of gene rearrangements and gene expression. Although successful amplification of DNA sequences has been carried out with DNA prepared from formalin-fixed, paraffin-embedded (FFPE) tissues, there are only a few reports regarding RNA analysis in this kind of material. We describe a procedure for RNA extraction from different types of FFPE tissues, involving digestion with proteinase K followed by guanidinium-thiocyanate acid phenol extraction and DNase I digestion. These RNA preparations are suitable for PCR analysis of mRNA and even of intronless genes. Furthermore, the universally expressed porphobilinogen deaminase mRNA proved to be useful as a positive control because of the lack of pseudogenes.

Journal ArticleDOI
15 Aug 1993-Blood
TL;DR: Results show that MO into MAC differentiation in vitro is associated with an enhanced capacity to synthesize 1,25(OH)2D3, a loss of 24,25-dihydroxyvitamin D3-synthesizing activity, and a decrease in the expression of VDR mRNA and protein.

Journal ArticleDOI
12 Feb 1993-Science
TL;DR: The spatial arrangement of TPP and FAD suggests that the oxidation of the oxyethyl intermediate does not occur by hydride displacement but rather by a two-step transfer of two electrons.
Abstract: Pyruvate oxidase from Lactobacillus plantarum is a tetrameric enzyme that decarboxylates pyruvate, producing hydrogen peroxide and the energy-storage metabolite acetylphosphate. Structure determination at 2.1 angstroms showed that the cofactors thiamine pyrophosphate (TPP) and flavin adenine dinucleotide (FAD) are bound at the carboxyl termini of six-stranded parallel beta sheets. The pyrophosphate moiety of TPP is bound to a metal ion and to a beta alpha alpha beta unit corresponding to an established sequence fingerprint. The spatial arrangement of TPP and FAD suggests that the oxidation of the oxyethyl intermediate does not occur by hydride displacement but rather by a two-step transfer of two electrons.

Journal ArticleDOI
M. Derrick1, D. Krakauer1, S. Magill1, B. Musgrave1  +459 moreInstitutions (37)
TL;DR: In this article, neutral current scattering of electrons and protons at square-root s = 296 GeV was observed in the ZEUS detector events with a large rapidity gap in the hadronic final state.

Journal ArticleDOI
TL;DR: The results show that gabexate mesilate was not effective in preventing complications and mortality in acute pancreatitis, and the effect of high doses of the low molecular weight protease inhibitor gabExate Mesilate on mortality and complications associated with moderate and severe acute Pancreatitis.

Journal ArticleDOI
TL;DR: Growth inhibition of Lemna gibba plantlets by the bleaching herbicide, SC‐0051 (2‐(2‐chloro‐4‐methanesulfonylbenzoyl)‐1,3‐cyclohexanedione)) was alleviated by the addition of homogentisic acid to the growth medium.

Journal ArticleDOI
TL;DR: Thiamin diphosphate binds to the three enzymes in a very similar fashion, and a general thiamin-binding fold can be revealed, despite considerable differences in quaternary structure and lack of overall sequence homology.

Journal ArticleDOI
M. Derrick1, D. Krakauer1, S. Magill1, B. Musgrave1  +464 moreInstitutions (37)
TL;DR: In this article, the first measurement of the F 2 structure function in neutral-current, deep inelastic scattering using the ZEUS detector at HERA, the ep colliding beam facility at DESY, was presented.

Journal ArticleDOI
TL;DR: The notochord is found to exert a ventralizing effect on the establishment of the dorso-ventral pattern in the somites, and a widening of the Pax-1-expressing domain in the sclerotome can be observed.
Abstract: The dorso-ventral pattern formation of the somites becomes manifest by the formation of the epithelially organized dorsal dermomyotome and the mesenchymal ventrally situated sclerotome. While the dermomyotome gives rise to dermis and muscle, the sclerotome differentiates into cartilage and bone of the axial skeleton. The onset of muscle differentiation can be visualized by immunohistochemistry for proteins associated with muscle contractility, e.g. desmin. The sclerotome cells and the epithelial ventral half of the somite express Pax-1, a member of a gene family with a sequence similarity to Drosophila paired-box-containing genes. In the present study, changes of Pax-1 expression were studied after grafting an additional notochord into the paraxial mesoderm region. The influence of the notochord and the floor-plate on dermomyotome formation and myotome differentiation has also been investigated. The notochord is found to exert a ventralizing effect on the establishment of the dorso-ventral pattern in the somites. Notochord grafts lead to a suppression of the formation and differentiation of the dorsal somitic derivatives. Simultaneously, a widening of the Pax-1-expressing domain in the sclerotome can be observed. In contrast, grafted roof-plate and aorta do not interfere with dorso-ventral patterning of the somitic derivatives.

Journal ArticleDOI
TL;DR: The inhibition of duck hepatitis B virus by antisense oligodeoxynucleotides in primary duck hepatocyte cultures in vitro as well as in DHBV‐infected Pekin ducks in vivo is reported.
Abstract: Antisense oligodeoxynucleotide strategies have been employed in a variety of eukaryotic systems both to understand normal gene function and to block gene expression. Pharmacologically, 'code blockers' are ideal agents for antitumour and antimicrobial treatments because of their specific mode of action. Here we report the inhibition of duck hepatitis B virus (DHBV) by antisense oligodeoxynucleotides in primary duck hepatocyte cultures in vitro as well as in DHBV-infected Pekin ducks in vivo. The most effective antisense oligodeoxynucleotide was directed against the 5' region of the pre-S gene and resulted in a complete inhibition of viral replication and gene expression in vitro and in vivo. These results demonstrate the application of antisense oligodeoxynucleotides in vivo and exemplify their potential as human antiviral therapeutics.

Journal ArticleDOI
13 Aug 1993-Cell
TL;DR: MOM22 appears to be a central component of the receptor complex, required for the transfer of preproteins from the receptors to the GIP, and it is speculated that the negatively charged domain of MOM22 is involved in theTransfer of positively charged signal sequences of pre Proteins.