julilili42/papers huggingface dataset:
DOCA-induced Phosphorylation of Glycogen Synthase Kinase 3ß
2006-01-01

Mineralocorticoid excess leads to cardiac fibrosis, a leading cause of morbidity and mortality. Cardiac hypertrophy and fibrosis are inhibited by the glycogen synthase kinase GSK3 which itself is a target of protein kinase B (PKB) and the serum and glucocorticoid inducible kinase SGK1. Phosphorylation of GSK3 by PKB or SGK1 inhibits GSK3 activity and should thus favour the development of cardiac hypertrophy and fibrosis. As SGK1 is transcriptionally upregulated by mineralocorticoids and has been recently shown to play an important role in the pathogenesis of mineralocorticoid-induced cardiac fibrosis, the present study explored whether mineralocorticoid excess had any effect on the phosphorylation status of the a and beta isoforms of GSK3. Western blotting using an antibody specific for the PKB/SGK1 consensus phosphorylation site in GSK3a/beta (serine 21 and 9 respectively) revealed an increase in GSK3a/beta phosphorylation in human embryonic kidney 293 (HEK293) cells overexpressing wild type SGK1, constitutively active SGK1, but not catalytically inactive SGK1. The effect of SGK1 was mimicked by PKB and SGK3. Furthermore, DOCA/high salt treatment of wild type mice induced a robust increase in cardiac GSK3beta phosphorylation and, to a much lesser extent, GSK3a phosphorylation. However, under this treatment GSK3beta phosphorylation was apparent even in mice lacking functional SGK1, indicating that the phosphorylation of GSK3beta was not exclusively mediated by this kinase. Despite similar cardiac GSK3beta phosphorylation cardiac fibrosis following DOCA/high salt treatment was significantly blunted in SGK1 knockout mice. In conclusion, mineralocorticoid excess leads to phosphorylation and thus inactivation of GSK3beta, an effect not only due to upregulation of SGK1 but as well due to activation of additional kinases. The inactivation of GSK3 may play a permissive role in the stimulation of cardiac fibrosis but may by itself not be sufficient to trigger cardiac fibrosis.
The ruthenocuprates: natural superconductor–ferromagnet multilayers
2006-01-01

The recently discovered ruthenocuprates have attracted great interest because of the microscopic coexistence of superconducting and ferromagnetic order. Typically, these materials become magnetically ordered at temperatures around 125–145 K and superconductivity sets in between 15 and 50 K. While superconductivity arises in the CuO 2 layers, the RuO 2 layers in between order magnetically. In this article we summarize some of the crystallographic, magnetic and superconducting properties of the ruthenocuprates, as obtained from investigations on polycrystalline samples as well as single crystals.
Functional Significance of the Kainate Receptor GluR6(M836I) Mutation that is Linked to Autism
2006-01-01

Previous studies revealed a linkage of the kainate receptor GluR6 with autism, a pervasive developmental disorder. Mutational screening in autistic patients disclosed the amino acid exchange M836I in a highly conserved domain of the cytoplasmic C-terminal region of GluR6. Here, we show that this mutation leads to GluR6 gain-of-function. By using the two-electrode voltage clamp technique we observed a significant increase of current amplitudes of mutant GluR6 compared to wild type GluR6. Western blotting of oocytes injected with mutant or wild type GluR6 cRNA and transfection of EGFP-tagged GluR6 receptors into COS-7 cells revealed an enhanced plasma membrane expression of GluR6(M836I) compared to wild type GluR6. Membrane expression of GluR6(M836I) but not of wild type GluR6 seems to be regulated by Rab11 as indicated by our finding that GluR6(M836I) but not wild type GluR6 showed increased current amplitudes and protein expression when coexpressed with Rab11. Furthermore, injection of GTP plus Rab11A protein into oocytes increased current amplitudes in GluR6(M836I) but not in wild type GluR6. By contrast, Rab5 downregulated the currents in oocytes expressing wild type GluR6 but had only little, statistically not significant effects on currents in oocytes expressing GluR6(M836I). Our data on altered functional properties of GluR6(M836I) provide a functional basis for the postulated linkage of GluR6 to autism. Furthermore, we identified new mechanisms determining the plasma membrane abundance of wild type GluR6 and GluR6(M836I).
Muscle Growth and Fiber Type Composition in Hind Limb Muscles during Postnatal Development in Pigs
2006-01-01

Rapid postnatal development in pigs is reflected by differentiation in skeletal muscle. This process depends on muscle function and demands, but a comprehensive overview of individual developmental characteristics of quickly growing leg muscles in pigs is still missing. This study focused on the development of 10 hind limb muscles in pigs. To determine these changes in mass, fiber type patterns and fiber diameters were analyzed 0, 2, 4, 7, 14, 28, 42, 56 and 400 days after birth. Generally, the proportion of slow fibers increased from birth to 8 weeks. Thereafter, only minor changes in muscle fiber type composition were observed. The majority of the muscles contained less then 10% slow-twitch fibers at birth, increasing to between 12 (Musculus vastus lateralis) and 38% (M. gastrocnemius medialis) in adult pigs. By contrast, postural muscles already had 20–30% slow fibers at birth, and this contribution increased up to 65% in adults (i.e. M. vastus intermedius). From birth to the 2nd week, only in slow fibers could activity of oxidative enzymes be detected. A differentiation of fast-twitch fibers into subtypes with high (comparable to type IIA) and low oxidative metabolism (equivalent to type IIB) occurred between the 2nd and 4th week of life. The ratio between type II fibers with high and low oxidative enzyme activity did not change markedly through development in any muscle, although there was a trend towards an increasing proportion of type IIA fibers in the soleus. In the majority of the muscles investigated, the fast-twitch fibers with low oxidative metabolism (IIB) obtained the largest cross-sectional area. In contrast, at birth no remarkable differences in the diameter of fast and slow fibers were found. The rapid increase in muscle mass compared to body mass reflects the high performance in meat production of the cross pig investigated.
Demonstration of the optical limiting effect for an hemiporphyrazine
2006-01-01

The hemiporphyrazine complex 9,22-bis(dibutoxy)hemiporphyrazinato chloroindium(III) (1) is one of the few examples for this class of compounds, which displays the nonlinear optical effect of reverse saturable absorption for nanosecond laser pulses in the visible spectrum. The high linear transmission combined with the fast switching into a strongly absorbing excited state in the same spectral range (400-650 nm), renders the studied hemiporphyrazine an ideal material for the passive shuttering of pulsed radiations.
Successful Verbal Retrieval in Elderly Subjects Is Related to Concurrent Hippocampal and Posterior Cingulate Activation
2006-01-01

&lt;i&gt;Objective:&lt;/i&gt; Memory decline and hippocampal atrophy are two major aspects of Alzheimer’s disease. Using a response-related fMRI design, we investigated the relationship between successful verbal retrieval and concurrent cerebral activation in elderly subjects in different stages of cognitive decline. We chose a correlational over the more traditional categorical approach to increase the power of detecting relevant activations. &lt;i&gt;Methods:&lt;/i&gt; Eleven subjects with Alzheimer’s disease, 21 elderly subjects with mild cognitive impairment, and 29 age-matched cognitively unimpaired subjects learned 180 nouns. While measuring brain activation with fMRI, the subjects had to classify these 180 learned plus 180 new distractor words as known or new. Response-related fMRI analysis was used to identify cerebral activation by correctly remembered words (hits) that correlated with retrieval success in the whole group. &lt;i&gt;Results:&lt;/i&gt; Successful verbal retrieval was significantly correlated with concurrent activation of the left hippocampus and posterior cingulate gyrus. &lt;i&gt;Conclusion:&lt;/i&gt; The study confirms the importance of adequate hippocampal function for successful verbal retrieval in the elderly. In addition, our study supports connectivity studies indicating a functional relationship between the hippocampus and the posterior cingulate gyrus during successful verbal retrieval in the elderly in different stages of cognitive decline.
Cell Volume Regulatory Mechanisms
2006-01-01

Prerequisites for cell survival include avoidance of excessive alterations of cell volume. Cells counterbalance the osmolarity due to cellular accumulation of organic substances by uneven distribution of inorganic ions. They extrude Na(+) in exchange for K(+) by the Na(+) /K(+) ATPase. The cell membrane is less permeable to Na(+) than to K(+) . The K(+) exit generates a cell-negative potential difference across the cell membrane which drives the exit of anions such as Cl(-) thus decreasing intracellular osmolarity. Upon cell swelling, cells release ions through activation of K(+) channels and/or anion channels, KCl-cotransport, or parallel activation of K(+) /H(+) exchange and Cl(-) /HCO-3 exchange. Upon cell shrinkage, cells accumulate ions through activation of Na(+) , K(+) , 2Cl(-) cotransport, Na(+) /H(+) exchange in parallel to Cl(-) /HCO3- exchange, or Na(+) channels. Na(+) taken up is extruded by the Na(+) /K(+) ATPase in exchange for K(+) . Shrunken cells further accumulate organic osmolytes. They generate sorbitol and glycerophosphorylcholine and monomeric amino acids by altered metabolism and take up myoinositol (inositol), betaine, taurine and amino acids by Na(+) coupled transport. They release osmolytes during cell swelling.
An innovative model for final-year students’ skills training course in internal medicine: ‘essentials from admission to discharge’
2006-01-01

Clerkships are generally seen as a very favourable learning environment for final-year students. However, in recent years the clinical experience of final-year students has been reported to decline progressively. It was decided, therefore, to introduce an innovative skills training model in internal medicine. Sixty final-year students received four consecutive days of training during their first week, consisting of three-hour sessions on each day. The skills training course reflected a patient history from admission to discharge and included all required routine procedures, typical forms/files and computer interactions. Acceptability was measured with self-administered surveys post-intervention and again 16 weeks later; self-assessment was measured pre-/post-intervention. The skills training course was well accepted by the students and led to a significant improvement in self-assessment. It was considered to be very helpful for work on the wards in both the immediate and the long-term retrospective evaluation. The final-year skills training course allows students to learn how to handle specific tools and applications for their work on the ward. It possesses face validity and is easy to integrate.
Experience increases the prepulse inhibition of the acoustic startle response in mice.
2006-01-01

The authors have previously shown that inhibition of the acoustic startle response by a prepulse increases when it is repetitively elicited over days. The present experiments show in C3H and C57 mice that this change is caused by an increase in prepulse inhibition (PPI) and not by a decrease in prepulse facilitation. This PPI increase is only evoked if prepulses and startle stimuli are repeatedly given in a temporally paired ("contingent") order, proposing an associative learning process. (Only in C57 mice, PPI was additionally increased by adaptation in the same, but not in a different, context). As an underlying mechanism for this PPI increase by experience, the authors hypothesize Hebbian plasticity of an inhibitory synapse.
Cranial variation inBairdemysturtles (podocnemididae: Miocene of the Caribbean region) and description of new material from Urumaco, Venezuela
2006-01-01

Synopsis Four new skulls referable to Bairdemys, from the Late Miocene Urumaco Formation in Venezuela, are described and compared with other specimens allocated to this genus. Several characters previously used to distinguish B. hartsteini (Cibao Formation, middle Miocene of Bayamon, Puerto Rico) from B. venezuelensis (Urumaco Formation) are present in the new Urumaco specimens, which show a mosaic of features from both species as originally diagnosed. Features of another Bairdemys skull from the Castillo Formation in the early Miocene of Lara State, Venezuela are unique, suggesting this is a new species, but poor preservation of known specimens prevents a formal diagnosis. In Bairdemys from Castillo the ventral surface of the secondary palate is proportionally larger in size, correlated with a smaller width of the internal nares and the distance between the foramina palatinae is relatively shorter. The ventral position of the quadrate in relation to the basisphenoid is far more posterior in the Castillo Bairdemys than in any other known specimen of this genus. The lower jaw of a Bairdemys specimen from Urumaco is described for the first time and compared to that of several Recent and fossil Pelomedusoides taxa. The specimen from Urumaco has a relatively large triturating surface, a large and wide dorsal opening of the fossa meckelii, a curved tomial ridge that slopes dorsally, a curved labial ridge that is less acute than in Podocnemis and no obvious accessory ridges comparable to ridges in Podocnemididae. Several shared features separate Bairdemys and Stereogenys from other fossil and Recent Podocnemididae.
Anomeric effect in the N–C–F moiety
2006-01-01

Experimental geometric structures and natural bond orbital (NBO) analyses demonstrate that anomeric effects may play an important role for structural and conformational properties of compounds containing the N–C–F moiety.
Allohormones inLumbricus terrestris? Mass spectrometry of the setal gland product indicates possible role of ubiquitin
2006-01-01

Summary In organisms containing sperm storage organs, sperm competition constitutes an important sexual selection factor. Sexual conflicts and unilateral manipulation of the reproductive physiology of the mating partner are common in the copulation behaviour of such organisms. In hermaphrodites, such conflicts escalate even more because of the identical interests of all individuals and the unique possibility to manipulate the degree of “femaleness” of the partner. This often results in bizarre reproductive tactics and mating behaviours. The simultaneous hermaphrodite Lumbricus terrestris uses specialized setae to pierce the partner's skin and inject a gland product during copulation. This happens in addition to, and is spatially distinct from, reciprocal sperm transfer. For the identification of bioactive compounds in the transferred secretion, comparative proteomic studies were performed, applying mass spectrometry and two-dimensional gel electrophoresis. Although initially targeting a substance with so-called “allohormone” characteristics, ubiquitin, a highly conserved 76 amino acid protein, could be identified as one of the predominant compounds. This contributes to recent findings concerning general roles of ubiquitin in reproductive events. One possible mechanism proposed, namely, that of labelling sperm for phagocytotic removal, is discussed.
Is it really that difficult to parse German?
2006-01-01

This paper presents a comparative study of probabilistic treebank parsing of German, using the Negra and TüBa-D/Z tree-banks. Experiments with the Stanford parser, which uses a factored PCFG and dependency model, show that, contrary to previous claims for other parsers, lexicalization of PCFG models boosts parsing performance for both treebanks. The experiments also show that there is a big difference in parsing performance, when trained on the Negra and on the TüBa-D/Z treebanks. Parser performance for the models trained on TüBa-D/Z are comparable to parsing results for English with the Stanford parser, when trained on the Penn treebank. This comparison at least suggests that German is not harder to parse than its West-Germanic neighbor language English.
Simulation of Application Strategies for Local Drug Delivery to the Inner Ear
2006-01-01

Local, rather than systemic, drug delivery to the inner ear is becoming more widely used to treat inner ear disorders. While many substances are undergoing preclinical and clinical studies, it is equally important to develop appropriate drug delivery systems. Pharmacokinetic studies are technically demanding in animals and almost impossible in humans. Computer simulations have helped establish the basic principles of drug distribution in the inner ear. The distribution of methylprednisolone in the guinea pig cochlea has been simulated for different drug delivery systems based on kinetic parameters established in prior studies. Results were compared for different rates of drug clearance from the middle ear. Absolute and relative drug levels in the perilymph were highly dependent on how long the drug remained in the middle ear. For a brief (30 min) application, the basal to apical drug gradient was higher than for longer delivery times. These findings show that controlling middle ear drug clearance is of critical importance.
Increased Glucose Uptake and Metabolism in Mesangial Cells Overexpressing Glucose Transporter 1 Increases Interleukin-6 and Vascular Endothelial Growth Factor Production: Role of AP-1 and HIF-1α
2006-01-01

Previous results indicate that enhanced glucose transporter (GLUT)1 expression mediates the deleterious effects of metabolic and hemodynamic perturbations leading to diabetic kidney disease. First screening for altered gene expression in GLUT1 overexpressing cells (GT1) by Affymetrix microarray analysis revealed upregulation of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) expression, which was verified by RT-PCR. Subsequently, IL-6 and VEGF protein production was more than 3-fold increased in the GT1 cells. This upregulation was independent from each other. Studies on the underlying transcriptional mechanisms by gelshift assays and siRNA approach implicated activation of AP-1 in the increased expression of both, IL-6 and VEGF. We found also increased nuclear protein levels of hypoxia-inducible factor (HIF)-1alpha and enhanced DNA binding activity to a hypoxia responsible element located in the VEGF promoter. Knock-down of HIF-1alpha reduced the VEGF expression to 50% with an additive effect of AP-1 gene silencing down to 24%. The IL-6 expression was not affected by reducing HIF-1alpha. In conclusion our results link increased GLUT1 levels leading to excess glucose metabolism under normoglycemic conditions and altered gene expression of pathogenetic factors involved in diabetic kidney disease.
Formal Performance Analysis and Simulation of UML/SysML Models for ESL Design
2006-01-01

UML2 and SysML try to adopt techniques known from software development to systems engineering. However, the focus has been put on modeling aspects until now and quantitative performance analysis is not adequately taken into account in early design stages of the system. In this paper, we present our approach for formal and simulation based performance analysis of systems specified with UML2/SysML. The basis of our analysis approach is the detection of communication that synchronize the control flow of the corresponding instances of the system and make the relationship explicit. Using this knowledge, we are able to determine a global timing behavior and violations of this effected by preset constraints. Hence, it is also possible to detect potential conflicts on shared communication resources if a specification of the target architecture is given. With these information it is possible to evaluate system models at an early design stage
Specificity of human cathepsin S determined by processing of peptide substrates and MHC class II-associated invariant chain
2006-01-01

Cathepsin S (CatS) is a lysosomal cysteine protease of the papain family, the members of which possess relatively broad substrate specificities. It has distinct roles in major histocompatibility complex (MHC) class II-associated peptide loading and in antigen processing in both the MHC class I and class II pathways. It may therefore represent a target for interference with antigen presentation, which could be of value in the therapy of (auto)immune diseases. To obtain more detailed information on the specificity of CatS, we mapped its cleavage site preferences at subsites S3-S1' by in vitro processing of a peptide library. Only five amino acid residues at the substrate's P2 position allowed for cleavage by CatS under time-limited conditions. Preferences for groups of amino acid residues were also observed at positions P3, P1 and P1'. Based on these results, we developed highly CatS-sensitive peptides. After processing of MHC class II-associated invariant chain (Ii), a natural protein substrate of CatS, we identified CatS cleavage sites in Ii of which a majority matched the amino acid residue preference data obtained with peptides. These observed cleavage sites in Ii might be of relevance for its in vivo processing by CatS.
De-standardised pathways to adulthood: European perspectives on informal learning in informal networks
2006-01-01

Becoming adult in the context of de-standardised life course transitions means new demands for the young women and men concerned. While those with higher social and cultural capital cope more easily with shaping individualised transitions, those with restricted resources and opportunities are under pressure of adaptation and at risk of exclusion. While de-standardisation can be regarded as a general trend, it takes varying shape across different European transition regimes whereby different regulative, normative and policy contexts of youth transitions are clustered. The article relates to the European YOYO study which has explored new learning demands and new learning strategies of young people in a comparative perspective. An exemplary illustration refers to the way in which young Germans make use of informal learning networks to cope with these demands. This micro perspective is related to the macro perspective by reflecting the scopes of individual agency provided by different transition regimes.