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Plasticity resembling spike-timing dependent synaptic plasticity: the evidence in human cortex
(2010)
Spike-timing dependent plasticity (STDP) has been studied extensively in a variety of animal models during the past decade but whether it can be studied at the systems level of the human cortex has been a matter of debate. Only recently newly developed non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) have made it possible to induce and assess timing dependent plasticity in conscious human subjects. This review will present a critical synopsis of these experiments, which suggest that several of the principal characteristics and molecular mechanisms of TMS-induced plasticity correspond to those of STDP as studied at a cellular level. TMS combined with a second phasic stimulation modality can induce bidirectional long-lasting changes in the excitability of the stimulated cortex, whose polarity depends on the order of the associated stimulus-evoked events within a critical time window of tens of milliseconds. Pharmacological evidence suggests an NMDA receptor mediated form of synaptic plasticity. Studies in human motor cortex demonstrated that motor learning significantly modulates TMS-induced timing dependent plasticity, and, conversely, may be modulated bidirectionally by prior TMS-induced plasticity, providing circumstantial evidence that long-term potentiation-like mechanisms may be involved in motor learning. In summary, convergent evidence is being accumulated for the contention that it is now possible to induce STDP-like changes in the intact human central nervous system by means of TMS to study and interfere with synaptic plasticity in neural circuits in the context of behavior such as learning and memory. Keywords: spike-timing dependent plasticity, long-term potentiation, long-term depression, paired associative stimulation, transcranial magnetic stimulation, human, cortex, translational neuroscience
Die Wissens'poetologie' bezeichnet eine 'Praxis', die ein Tableau verschiedener Wissensfelder freilegt, um die Bedingungen der historisch-epistemologischen Möglichkeiten verschiedener Wissensordnungen zu hinterfragen und zu untersuchen. Doch wie werden diese Praktiken 'in concreto' von der Literatur vollzogen? Zwei mögliche wissenspoetologische Praktiken sollen anhand der Schriften Walter Benjamins und Jorge Luis Borges' verdeutlicht werden, um sie weiterführend als Paradigma für komparatistische Nachforschungen in der Wissenspoetologie zu verwenden: die 'Fiktionalisierung' und das 'Experiment'.
Doppeltgänger — man fasst diesen Begriff bei Jean Paul gerne im heutigen Sinne auf, also als Beschreibung zweier Menschen, die sich äußerlich gleichen und daher von dritten miteinander verwechselt werden. Das 18. und frühe 19. Jahrhundert hat jedoch vor allem die Dimension des "geistige[n] Doppeltgänger[s]" im Blick, also die psychische, ja psychopathologische Innenansicht einer solchen Verwechslung. Es handelt sich bei einem oder mehreren Doppeltgängern dementsprechend um "Leute, die sich selber sehen" oder genauer:'um "eine Person, von verbrannter Embildungskraft, welche wahnt, daß sie doppelt zu sehen sei, oder zu einer und derselben Zeit an zwei verschiedenen Orten zugleich sei".'
The asymmetric unit of the title compound, [K(C5HF6N2)(H2O)2]n, is composed of two 3,5-bis(trifluoromethyl)pyrazolide anions, two potassium cations and four water molecules. The water molecules and 3,5-bis(trifluoromethyl)pyrazolide anions act as bridges between the potassium cations. Each potassium cation is surrounded by four O atoms [K—O = 2.705 (3)–2.767 (3) Å] and four F atoms [K—F = 2.870 (7)–3.215 (13) Å]. The water molecules and the 3,5-bis(trifluoromethyl)pyrazolide anions are connected by O—H ... N hydrogen bonds, forming layers in the ab plane. All –CF3 groups show rotational disorder between two orientations each.
Background: Autism spectrum disorders (ASDs) are a group of highly heritable neurodevelopmental disorders which are characteristically comprised of impairments in social interaction, communication and restricted interests/behaviours. Several cell adhesion transmembrane leucine-rich repeat (LRR) proteins are highly expressed in the nervous system and are thought to be key regulators of its development. Here we present an association study analysing the roles of four promising candidate genes - LRRTM1 (2p), LRRTM3 (10q), LRRN1 (3p) and LRRN3 (7q) - in order to identify common genetic risk factors underlying ASDs.
Methods: In order to gain a better understanding of how the genetic variation within these four gene regions may influence susceptibility to ASDs, a family-based association study was undertaken in 661 families of European ancestry selected from four different ASD cohorts. In addition, a case-control study was undertaken across the four LRR genes, using logistic regression in probands with ASD of each population against 295 ECACC controls.
Results: Significant results were found for LRRN3 and LRRTM3 (P < 0.005), using both single locus and haplotype approaches. These results were further supported by a case-control analysis, which also highlighted additional SNPs in LRRTM3.
Conclusions: Overall, our findings implicate the neuronal leucine-rich genes LRRN3 and LRRTM3 in ASD susceptibility.
Background: Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are produced during hemorrhagic shock and resuscitation (H/R), which may contribute to multiple organ failure. The AIM of this study was to test the hypothesis that green tea (Camellia sinenesis) extract containing 85% polyphenols decreases injury after H/R in rats by scavenging ROS and RNS. Method: S: Female Sprague Dawley rats were given 100 mg polyphenol extract/kg body weight or vehicle 2 h prior to hemorrhagic shock. H/R was induced by two protocols: 1) withdrawal of blood to a mean arterial pressure of 40 mm Hg followed by further withdrawals to decrease blood pressure progressively to 28 mm Hg over 1 h (severe), and 2) withdrawal of blood to a sustained hypotension of 40 mm Hg for 1 h (moderate). Rats were then resuscitated over 1 h with 60% of the shed blood volume plus twice the shed blood volume of lactated Ringer's solution. Serum samples were collected at 10 min and 2 h after resuscitation. At 2 or 18 h, livers were harvested for cytokine and 3-nitrotyrosine quantification, immunohistochemical detection of 4-hydroxynonenol (4-HNE) and inducible nitric oxide synthase (iNOS) protein expression. Results: After severe H/R, 18-h survival increased from 20% after vehicle to 70% after polyphenols (p<0.05). After moderate H/R, survival was greater (80%) and not different between vehicle and polyphenols. In moderate H/R, serum alanine aminotransferase (ALT) increased at 10 min and 2 h postresuscitation to 345 and 545 IU/L, respectively. Polyphenol treatment blunted this increase to 153 and 252 IU/L at 10 min and 2 h (p<0.01). Polyphenols also blunted increases in liver homogenates of TNFalpha (7.0 pg/mg with vehicle vs. 4.9 pg/mg with polyphenols, p<0.05), IL-1beta (0.80 vs. 0.37 pg/mg, p<0.05), IL-6 (6.9 vs. 5.1 pg/mg, p<0.05) and nitrotyrosine (1.9 pg/mg vs. 0.6 pg/mg, p<0.05) measured 18 h after H/R. Hepatic 4-HNE immunostaining indicative of lipid peroxidation also decreased from 4.8% after vehicle to 1.5% after polyphenols (p<0.05). By contrast, polyphenols did not block increased iNOS expression at 2 h after H/R. CONCLUSION: Polyphenols decrease ROS/RNS formation and are beneficial after hemorrhagic shock and resuscitation.
This paper presents a study on a population of Pulsatilla patens conducted in 2009 in the Natura 2000 wildlife refuge called "Grasslands in the Military Training Grounds in Orzysz" in the Masurian Lake District (NE Poland). The purpose of the study was to determine the population structure of Pulsatilla patens, especially with regard to abundance, density, and percentage of life cycle stages in the total population. Correlations were examined between these population features and selected environmental characteristics including cover of phanerogams, cryptogams, litter, and bare soil. For the evaluation of the linear relationship between the variables, Spearman's correlation coefficient was used. In order to identify the factors that have significant influence on the values of the dependent variables, a multiple regression analysis was performed. In total, 316 individuals of Pulsatilla patens were recorded: 62 flower ing adults, 202 vegetative adults and 52 juveniles. The number of flowers per individual varied from one to 12, the average being three flowers. Most individuals occurred in dry heath, and the smallest number of individuals was found in pine forest. The mean density per habitat ranged from one to 11 individuals per 4 m2. Increased cover of phanerogams and cryptogams caused a decrease in the density of Pulsatilla patens individuals.
Turmfalke (Falco tinnunculus) und Schleiereule (Tyto alba)
sind seit Jahrhunderten avifaunistischer Bestandteil der Kulturräume
Süddeutschlands, wobei deren jährliche Reproduktionsraten
erheblichen Schwankungen unterliegen und bei
beiden Arten nicht synchron verlaufen müssen. Diese Arbeit
beruht auf Untersuchungen der Populationsentwicklung von
Schleiereule und Turmfalke, die über zehn Jahre auf einer
Probefläche in der Region Kraichgau (Südwestdeutschland)
durchgeführt wurden. Unsere Daten belegen einen positiven
Effekt der Schaffung neuer bzw. der Optimierung alter Brutplätze
auf die Populationsentwicklung beider Vogelarten. 81 %
der gebäudebrütenden Turmfalken und 99 % der Schleiereulen
brüteten in künstlichen Nisthilfen. Die Brutpaardichte der
Schleiereule schwankte von 1,4 Paaren/100 km2 bis 8,6
Paaren/100km2, die des Turmfalken von 6,6 Paaren/100 km2
bis 19,7 Paaren/100 km2. Im Mittel lag die Reproduktionsrate
der Schleiereule während des Untersuchungszeitraumes bei
4,7 Jungvögeln pro erfolgreicher Erstbrut, die des Turmfalken
ebenfalls bei 4,7 Jungvögeln pro erfolgreicher Brut. Für die
Schleiereule zeigte sich aktuell im Vergleich zu früheren Perioden
keine direkte Abhängigkeit der Brutpopulation von der
Anzahl der Schneetage des vorausgegangenen Winters. Beim
Turmfalken fiel eine ausgeprägte Jugenddispersion auf. Unsere
Daten sprechen zudem für eine Brutplatzkonkurrenz zwischen
Dohle, Turmfalke und Schleiereule im Siedlungsraum.
Posljedice globalizacijskih procesa vidljive su i u jeziku kao tendencija k internacionalizaciji. Internacionalizacija, ili možda preciznije angloamerikanizacija, zahvatila je sve jezike modernoga svijeta. Hrvatski jezik nije iznimka. U ovom ćemo radu spomenuti samo neke od posljedica internacionalizacije, i to na leksičkoj, tvorbenoj i semantičkoj razini.
The article analyses the early novels stillborn, Terminifera und Magma by Michael Stavarič in respect of their compliance with the theory of postmodern novels. The analysis concludes that the works of th e academically educated writer correspond in very high proportions to the theory and attitudes of post-modernism.
Potentiation of glycine-gated NR1/NR3A NMDA receptors relieves Ca2+-dependent outward rectification
(2010)
Glycine has diverse functions within the mammalian central nervous system. It inhibits postsynaptic neurons via strychnine-sensitive glycine receptors (GlyRs) and enhances neuronal excitation through co-activation of N-methyl-D-aspartate (NMDA) receptors. Classical Ca2+-permeable NMDA receptors are composed of glycine-binding NR1 and glutamate-binding NR2 subunits, and hence require both glutamate and glycine for efficient activation. In contrast, recombinant receptors composed of NR1 and the glycine binding NR3A and/or NR3B subunits lack glutamate binding sites and can be activated by glycine alone. Therefore these receptors are also named “excitatory glycine receptors”. Co-application of antagonists of the NR1 glycine-binding site or of the divalent cation Zn2+ markedly enhances the glycine responses of these receptors. To gain further insight into the properties of these glycine-gated NMDA receptors, we investigated their current-voltage (I–V) dependence. Whole-cell current-voltage relations of glycine currents recorded from NR1/NR3B and NR1/NR3A/NR3B expressing oocytes were found to be linear under our recording conditions. In contrast, NR1/NR3A receptors displayed a strong outwardly rectifying I–V relation. Interestingly, the voltage-dependent inward current block was abolished in the presence of NR1 antagonists, Zn2+ or a combination of both. Further analysis revealed that Ca2+ (1.8 mM) present in our recording solutions was responsible for the voltage-dependent inhibition of ion flux through NR1/NR3A receptors. Since physiological concentrations of the divalent cation Mg2+ did not affect the I–V dependence, our data suggest that relief of the voltage-dependent Ca2+ block of NR1/NR3A receptors by Zn2+ may be important for the regulation of excitatory glycinergic transmission, according to the Mg2+-block of conventional NR1/NR2 NMDA receptors. Keywords: NMDA receptor, excitatory glycine receptor, voltage block, NR3 subunit, supralinear potentiation, Zn2+, NR1 antagonist, ligand-binding domain
Background: Current conventional vaccination approaches do not induce potent CD8 T-cell responses for fighting mostly variable viral diseases such as influenza, avian influenza viruses or HIV. Following our recent study on vaccine penetration by targeting of vaccine to human hair follicular ducts surrounded by Langerhans cells, we tested in the first randomized Phase-Ia trial based on hair follicle penetration (namely transcutaneous route) the induction of virus-specific CD8 T cell responses. Methods and Findings: We chose the inactivated influenza vaccine – a conventional licensed tetanus/influenza (TETAGRIP®) vaccine – to compare the safety and immunogenicity of transcutaneous (TC) versus IM immunization in two randomized controlled, multi-center Phase I trials including 24 healthy-volunteers and 12 HIV-infected patients. Vaccination was performed by application of inactivated influenza vaccine according to a standard protocol allowing the opening of the hair duct for the TC route or needle-injection for the IM route. We demonstrated that the safety of the two routes was similar. We showed the superiority of TC application, but not the IM route, to induce a significant increase in influenza-specific CD8 cytokine-producing cells in healthy-volunteers and in HIV-infected patients. However, these routes did not differ significantly for the induction of influenza-specific CD4 responses, and neutralizing antibodies were induced only by the IM route. The CD8 cell response is thus the major immune response observed after TC vaccination. Conclusions: This Phase Ia clinical trial (Manon05) testing an anti-influenza vaccine demonstrated that vaccines designed for antibody induction by the IM route, generate vaccine-specific CD8 T cells when administered transcutaneously. These results underline the necessity of adapting vaccination strategies to control complex infectious diseases when CD8 cellular responses are crucial. Our work opens up a key area for the development of preventive and therapeutic vaccines for diseases in which CD8 cells play a crucial role.
The continuous progress in the structural and functional characterization of aquaporins increasingly attracts attention to study their roles in certain mammalian diseases. Although several structures of aquaporins have already been solved by crystallization, the challenge of producing sufficient amounts of functional proteins still remains. CF (cell free) expression has emerged in recent times as a promising alternative option in order to synthesize large quantities of membrane proteins, and the focus of this report was to evaluate the potential of this technique for the production of eukaryotic aquaporins. We have selected the mouse aquaporin 4 as a representative of mammalian aquaporins. The protein was synthesized in an E. coli extract based cell-free system with two different expression modes, and the efficiencies of two modes were compared. In both, the P-CF (cell-free membrane protein expression as precipitate) mode generating initial aquaporin precipitates as well as in the D-CF (cell-free membrane protein expression in presence of detergent) mode, generating directly detergent solubilized samples, we were able to obtain mg amounts of protein per ml of cell-free reaction. Purified aquaporin samples solubilized in different detergents were reconstituted into liposomes, and analyzed for the water channel activity. The calculated Pf value of proteoliposome samples isolated from the D-CF mode was 133 µm/s at 10°C, which was 5 times higher as that of the control. A reversible inhibitory effect of mercury chloride was observed, which is consistent with previous observations of in vitro reconstituted aquaporin 4. In this study, a fast and convenient protocol was established for functional expression of aquaporins, which could serve as basis for further applications such as water filtration.
U prilogu se s kontrastivnog aspekta analiziraju frazemi hrvatskoga i češkoga jezika kojima je sastavnica zoonim. Životinja je još od pradavnih vremena najbliži čovjekov suputnik. U svim se narodima životinjama pripisuju simbolična značenja i ljudske osobine i to najčešće one negativne što ćemo i pokušati dokazati ovim prilogom. Naime, ljudi su kroz povijest pripisivali životinjama određene stereotipe. Tako se pozitivno određuju domaće životinje i to one od kojih čovjek ima više koristi, za razliku od divljih prema kojima je puno kritičniji i skloniji negativnome određenju. S obzirom na to da zoonimska frazeologija obuhvaća širok dijapazon različitih značenja u ovome ćemo se prilogu baviti onim frazemima koji svojim značenjem ulaze u koncept ljudskih osobina, stanja, izgleda, načina kretanja te odnosa prema jelu i piću. Pri tome se objašnjava i simbolika pojedine životinje jer se time razumije i pozadinska slika pojedina frazema. Također u prilogu se provodi i kontrastivna analiza izdvojenih hrvatskih i čeških frazema s obzirom na navedene koncepte te se utvrđuju podudarnosti i razlike.
Ključne riječi: frazem; zoonim; frazemska pozadinska slika; kontrastivna analiza; hrvatski jezik; češki jezik
WE STUDY WHETHER PRIVATE EQUITY (PE) FIRMS HAVE A POSITIVE IMPACT ON THE FINANCIAL PERFORMANCE OF THEIR GERMAN PORTFOLIO COMPANIES BEFORE AND AFTER THE IPO. OUR EMPIRICAL ANALYSIS IS BASED ON A UNIQUE AND LARGE DATASET OF ALL IPOS IN GERMANY BETWEEN 2000 AND 2007. WE FIND THAT PE FIRMS SELECT COMPANIES WITH BELOW AVERAGE PERFORMANCE AND THEN IMPROVE PERFORMANCE SUBSTANTIALLY UNTIL THE IPO DATE AND IN MANY CASES ALSO THEREAFTER. THIS IMPLIES THAT PE FIRMS FILL A VOID ALSO IN GERMAN FINANCIAL MARKETS AND THAT THEY WILL ALSO PLAY A FUTURE ROLE IN FINANCING GERMAN ENTERPRISES.
Fasst man das Konzept der Katharsis als die wohltuende Auflösung eines durch eine Erzählung ausgelösten, emotionalen Spannungszustandes auf, dann lässt sich wohl behaupten, dass diese nach wie vor das aristotelisch-klassische Ziel des modernen Mainstream Kinos ist. Das Besondere an dem Film The Reader ist nun, dass diese Katharsis nicht nur ein latent verfolgtes Ziel des Filmes, d.h. ein unbewusstes Nebenprodukt eines Happy Ends ist, sondern gleichzeitig auch expliziter Teil der Erzählung (und somit eine begriffliche Ausweitung erfährt): Ist eine Katharsis angesichts der Schrecken von Auschwitz überhaupt möglich? Die folgende Deutung glaubt, dass der Film diese Frage versucht zu bejahen, indem er auf die Möglichkeiten eines ‚poetischen Kinos’ verweist. Diese bestehen nicht zuletzt in der Symbolisierung des ‚Unaussprechlichen’, die zwar keine rationale, dafür aber eine emotionale Integration der NS-Vergangenheit zu leisten können beansprucht.
Anhand des Fallbeispiels studiumdigitale, der zentralen eLearning-Einrichtung der Goethe-Universität Frankfurt, werden verschiedene Thesen zur Einrichtung und Entwicklung einer so genannten Third Space-Einrichtung dargelegt, die einerseits den Erfolg und das Überleben einer Einrichtung wie auch ihre Fortentwicklung betreffen. Der Schwerpunkt liegt dabei auf der Ausgestaltung der Austauschbeziehung der Einrichtung zu ihren ‚Kunden’, den Lehrenden, zu ihren Nachbareinrichtungen und sowie der Definition und Ausprägung der Aufgaben der Institution.
On August 13, 2010 Horst Schuller, university professor, former head of the German Studies Department of the University of Sibiu, Romanian-born German critic and literary historian reached the age of 70 years. The present article pays homage to the well-known scientist at reaching the venerable age.
Programmatik und Verfahren des Direct Cinema (mit besonderem Augenmerk auf Don Alan Pennebaker)
(2010)
Das amerikanische Direct Cinema, wie es 1960 unter der Leitung von Robert Drew mit PRIMARY, dem ersten Film der Gruppe um Richard Leacock und D.A. Pennebaker, entstanden war, gab rasch dem amerikanischen Dokumentarfilm und bald auch der internationalen Szene revolutionierende und revitalisierende Impulse. Es basiert auf der Erfindung Leacocks und anderer, mithilfe der Pilotton-Technik ein tragbares Tonaufzeichnungsgerät mit der 16mm-Kamera zu synchronisieren. Damit war der Dokumentarfilm sozusagen freigesetzt, man konnte den gefilmten Personen überallhin folgen und den authentischen Ton vor Ort aufzeichnen, während zuvor ein Tonstudio nötig war.
The title compound, C15H14N2O4, has a trans–gauche [O/C/C/C–O/C/C/C] (TG) conformation. The angle between the planes of aromatic rings is 76.4 (3)°. The crystal structure is stabilized by van der Waals interactions and C—H ... O hydrogen bonds. The crystal used was a non-merohedral twin with a fractional contribution of the minor component of 0.443 (5).
The title compound. C15H14N2O4, (I), has a gauche–gauche (O/C/C/C—O/C/C/C or GG) conformation and is a positional isomer of propane-1,3-diyl bis(pyridine-3-carboxylate), (II). The molecule of (I) lies on a twofold rotation axis, which passes through the central C atom of the aliphatic chain, giving one half-molecule per asymmetric unit. There is excellent agreement of the geometric parameters of (I) and (II). The most obvious differences between them are the O/C/C/C—O/C/C/C torsion angles [56.6 (2)° in (I) and 174.0 (3)/70.2 (3)° in (II) for GG and TG conformations, respectively] and the dihedral angle between the planes of the aromatic rings [80.3 (10)° in (I) and 76.5 (3)° in (II)]. The crystal structure is stabilized by weak C—H ... N and C—H ... O hydrogen bonding.
Proteins can be acetylated at the alpha-amino group of the N-terminal amino acid (methionine or the penultimate amino acid after methionine removal) or at the epsilon-amino group of internal lysines. In eukaryotes the majority of proteins are N-terminally acetylated, while this is extremely rare in bacteria. A variety of studies about N-terminal acetylation in archaea have been reported recently, and it was revealed that a considerable fraction of proteins is N-terminally acetylated in haloarchaea and Sulfolobus, while this does not seem to apply for methanogenic archaea. Many eukaryotic proteins are modified by differential internal acetylation, which is important for a variety of processes. Until very recently, only two bacterial proteins were known to be acetylation targets, but now 125 acetylation sites are known for E. coli. Knowledge about internal acetylation in archaea is extremely limited; only two target proteins are known, only one of which--Alba--was used to study differential acetylation. However, indications accumulate that the degree of internal acetylation of archaeal proteins might be underestimated, and differential acetylation has been shown to be essential for the viability of haloarchaea. Focused proteomic approaches are needed to get an overview of the extent of internal protein acetylation in archaea.
Activation of Notch1 signaling in neural progenitor cells (NPCs) induces self-renewal and inhibits neurogenesis. Upon neuronal differentiation, NPCs overcome this inhibition, express proneural genes to induce Notch ligands, and activate Notch1 in neighboring NPCs. The molecular mechanism that coordinates Notch1 inactivation with initiation of neurogenesis remains elusive. Here, we provide evidence that Prox1, a transcription repressor and downstream target of proneural genes, counteracts Notch1 signaling via direct suppression of Notch1 gene expression. By expression studies in the developing spinal cord of chick and mouse embryo, we showed that Prox1 is limited to neuronal precursors residing between the Notch1+ NPCs and post-mitotic neurons. Physiological levels of Prox1 in this tissue are sufficient to allow binding at Notch1 promoter and they are critical for proper Notch1 transcriptional regulation in vivo. Gain-of-function studies in the chick neural tube and mouse NPCs suggest that Prox1-mediated suppression of Notch1 relieves its inhibition on neurogenesis and allows NPCs to exit the cell cycle and differentiate. Moreover, loss-of-function in the chick neural tube shows that Prox1 is necessary for suppression of Notch1 outside the ventricular zone, inhibition of active Notch signaling, down-regulation of NPC markers, and completion of neuronal differentiation program. Together these data suggest that Prox1 inhibits Notch1 gene expression to control the balance between NPC self-renewal and neuronal differentiation.
Quantification of circulating endothelial progenitor cells using the modified ISHAGE protocol
(2010)
Aims: Circulating endothelial progenitor cells (EPC), involved in endothelial regeneration, neovascularisation, and determination of prognosis in cardiovascular disease can be characterised with functional assays or using immunofluorescence and flow cytometry. Combinations of markers, including CD34+KDR+ or CD133+KDR+, are used. This approach, however may not consider all characteristics of EPC. The lack of a standardised protocol with regards to reagents and gating strategies may account for the widespread inter-laboratory variations in quantification of EPC. We, therefore developed a novel protocol adapted from the standardised so-called ISHAGE protocol for enumeration of haematopoietic stem cells to enable comparison of clinical and laboratory data. Methods and Results: In 25 control subjects, 65 patients with coronary artery disease (CAD; 40 stable CAD, 25 acute coronary syndrome/acute myocardial infarction (ACS)), EPC were quantified using the following approach: Whole blood was incubated with CD45, KDR, and CD34. The ISHAGE sequential strategy was used, and finally, CD45dimCD34+ cells were quantified for KDR. A minimum of 100 CD34+ events were collected. For comparison, CD45+CD34+ and CD45-CD34+ were analysed simultaneously. The number of CD45dimCD34+KDR+ cells only were significantly higher in healthy controls compared to patients with CAD or ACS (p = 0.005 each, p<0.001 for trend). An inverse correlation of CD45dimCD34+KDR+ with disease activity (r = -0.475, p<0.001) was confirmed. Only CD45dimCD34+KDR+ correlated inversely with the number of diseased coronaries (r = -0.344; p<0.005). In a second study, a 4-week de-novo treatment of atorvastatin in stable CAD evoked an increase only of CD45dimCD34+KDR+ EPC (p<0.05). CD45+CD34+KDR+ and CD45-CD34+KDR+ were indifferent between the three groups. Conclusion: Our newly established protocol adopted from the standardised ISHAGE protocol achieved higher accuracy in EPC enumeration confirming previous findings with respect to the correlation of EPC with disease activity and the increase of EPC during statin therapy. The data of this study show the CD45dim fraction to harbour EPC.
O presente artigo oferece um breve panorama acerca do ensino da língua alemã no Brasil. Seguindo os conceitos e dimensões de bilinguismo e bilingualidade , identifica o ensino de língua alemã como segunda língua e trata do aspecto da interculturalidade restrito à análise da prática em duas escolas bilíngues do Rio de Janeiro, onde a língua/cultura alemã é a segunda língua.(L2) Propõese uma reflexão sobre a questão da interculturalidade no âmbito da comemoração de datas festivas em escolas bilíngues. Dentro dessa temática e no contexto escolar bilíngue, delimitamos o estudo a eventos comemorativos como a Páscoa, marcados pela distribuição de ovinhos de Páscoa/Ostereier. O estudo baseia-se em uma perspectiva sociocultural da linguagem e ressalta as relações entre língua, identidade e estrutura social.
Background: A delta and C fibers are the major pain-conducting nerve fibers, activate only partly the same brain areas, and are differently involved in pain syndromes. Whether a stimulus excites predominantly A delta or C fibers is a commonly asked question in basic pain research but a quick test was lacking so far. Methodology/Principal Findings: Of 77 verbal descriptors of pain sensations, "pricking", "dull" and "pressing" distinguished best (95% cases correctly) between A delta fiber mediated (punctate pressure produced by means of von Frey hairs) and C fiber mediated (blunt pressure) pain, applied to healthy volunteers in experiment 1. The sensation was assigned to A delta fibers when "pricking" but neither "dull" nor "pressing" were chosen, and to C fibers when the sum of the selections of "dull" or "pressing" was greater than that of the selection of "pricking". In experiment 2, with an independent cohort, the three-descriptor questionnaire achieved sensitivity and specificity above 0.95 for distinguishing fiber preferential non-mechanical induced pain (laser heat, exciting A delta fibers, and 5-Hz electric stimulation, exciting C fibers). Conclusion: A three-item verbal rating test using the words "pricking", "dull", and "pressing" may provide sufficient information to characterize a pain sensation evoked by a physical stimulus as transmitted via A delta or via C fibers. It meets the criteria of a screening test by being easy to administer, taking little time, being comfortable in handling, and inexpensive while providing high specificity for relevant information.
Background: R-flurbiprofen, one of the enantiomers of flurbiprofen racemate, is inactive with respect to cyclooxygenase inhibition, but shows analgesic properties without relevant toxicity. Its mode of action is still unclear. Methodology/Principal Findings: We show that R-flurbiprofen reduces glutamate release in the dorsal horn of the spinal cord evoked by sciatic nerve injury and thereby alleviates pain in sciatic nerve injury models of neuropathic pain in rats and mice. This is mediated by restoring the balance of endocannabinoids (eCB), which is disturbed following peripheral nerve injury in the DRGs, spinal cord and forebrain. The imbalance results from transcriptional adaptations of fatty acid amide hydrolase (FAAH) and NAPE-phospholipase D, i.e. the major enzymes involved in anandamide metabolism and synthesis, respectively. R-flurbiprofen inhibits FAAH activity and normalizes NAPE-PLD expression. As a consequence, R-Flurbiprofen improves endogenous cannabinoid mediated effects, indicated by the reduction of glutamate release, increased activity of the anti-inflammatory transcription factor PPAR gamma and attenuation of microglia activation. Antinociceptive effects are lost by combined inhibition of CB1 and CB2 receptors and partially abolished in CB1 receptor deficient mice. R-flurbiprofen does however not cause changes of core body temperature which is a typical indicator of central effects of cannabinoid-1 receptor agonists. Conclusion: Our results suggest that R-flurbiprofen improves the endogenous mechanisms to regain stability after axonal injury and to fend off chronic neuropathic pain by modulating the endocannabinoid system and thus constitutes an attractive, novel therapeutic agent in the treatment of chronic, intractable pain.
Background: Early inner ear development requires the strict regulation of cell proliferation, survival, migration and differentiation, coordinated by the concerted action of extrinsic and intrinsic factors. Deregulation of these processes is associated with embryonic malformations and deafness. We have shown that insulin-like growth factor I (IGF-I) plays a key role in embryonic and postnatal otic development by triggering the activation of intracellular lipid and protein kinases. RAF kinases are serine/threonine kinases that regulate the highly conserved RAS-RAF-MEK-ERK signaling cascade involved in transducing the signals from extracellular growth factors to the nucleus. However, the regulation of RAF kinase activity by growth factors during development is complex and still not fully understood.
Methodology/Principal Findings: By using a combination of qRT-PCR, Western blotting, immunohistochemistry and in situ hybridization, we show that C-RAF and B-RAF are expressed during the early development of the chicken inner ear in specific spatiotemporal patterns. Moreover, later in development B-RAF expression is associated to hair cells in the sensory patches. Experiments in ex vivo cultures of otic vesicle explants demonstrate that the influence of IGF-I on proliferation but not survival depends on RAF kinase activating the MEK-ERK phosphorylation cascade. With the specific RAF inhibitor Sorafenib, we show that blocking RAF activity in organotypic cultures increases apoptosis and diminishes the rate of cell proliferation in the otic epithelia, as well as severely impairing neurogenesis of the acoustic-vestibular ganglion (AVG) and neuron maturation.
Conclusions/Significance: We conclude that RAF kinase activity is essential to establish the balance between cell proliferation and death in neuroepithelial otic precursors, and for otic neuron differentiation and axonal growth at the AVG.
Rani razvoj goranskih govora
(2010)
U radu se razmatra povijest hrvatskih govora u Gorskome kotaru, koji se obično smatraju kajkavskim govorima. Obrađuju se različite promjene u akcentuaciji, konsonantizmu i vokalizmu do približno 16. stoljeća. One se uspoređuju sa sličnim promjenama u susjednim kajkavskim, slovenskim, čakavskim i štokavskim dijalektima. Najstarije nam izoglose pokazuju da goranske govore ne možemo smatrati doseljenim izdaleka ili miješanim. Moramo ih smjestiti u Gorski kotar već prije otomanskih nadiranja u 15. i 16. stoljeću. Raspravlja se o tome da je Gorski kotar dijalektno područje kroz koje teče više izoglosa koje postaju razumljive kad smještamo ovo područje u perspektivu okolnih južnoslavenskih narječja.
Raoul Sage
(2010)
Raoul Sage
(2010)
Raoul Sage
(2010)
We report the first measurements of 1,1,1,2,3,3,3-heptafluoropropane (HFC-227ea), a substitute for ozone depleting compounds, in remote regions of the atmosphere and present evidence for its rapid growth. Observed mixing ratios ranged from below 0.01 ppt in deep firn air to 0.59 ppt in the northern mid-latitudinal upper troposphere. Firn air samples collected in Greenland were used to reconstruct a history of atmospheric abundance. Year-on-year increases were deduced, with acceleration in the growth rate from 0.026 ppt per year in 2000 to 0.057 ppt per year in 2007. Upper tropospheric air samples provide evidence for a continuing growth until late 2009. Fur- thermore we calculated a stratospheric lifetime of 370 years from measurements of air samples collected on board high altitude aircraft and balloons. Emission estimates were determined from the reconstructed atmospheric trend and suggest that current "bottom-up" estimates of global emissions for 2005 are too high by more than a factor of three.
Based on newly collected samples and data from the literature, an updated list of the marine bivalves of the Cape Verde Islands is presented. From 2004 to 2006, collections were made at 22 sampling points in the islands of Santiago, São Vicente, Santa Luzia, São Nicolau, Boavista and Maio. Using qualitative and direct sampling methods, 39 species of bivalves, belonging to 20 families, were identified. Families most represented were Veneridae (6 species), Cardiidae (5 species), Arcidae (4 species) and Mytilidae (4 species). Islands with the largest diversity of species were São Vicente (30 species) and Santiago (23 species), probably due to the larger number of sample points (64% of total). Six species not previously reported from the archipelago were collected, i.e. Irus irus, Venus declivis, Timoclea ovata, Diplodonta rotundata, Plagiocardium papillosum and Tagelus adansoni. Corbicula fluminea, supposedly a man assisted introduction, was also collected.
Based on both stranding and sighting records, recent data on the status and distribution of whales and dolphins in the Cape Verde Islands are presented, including records of four taxa new to the archipelago, viz. Common minke whale Balaenoptera acutorostrata, Dwarf sperm whale Kogia sima, beaked whale Mesoplodon cf. europaeus and False killer whale Pseudorca crassidens. Distribution elsewhere in the tropical eastern Atlantic and some taxonomic issues are discussed.
Observations on the longevity and ecology of Isopogon prostratus McGill. (Proteaceae) based on 1985 and 2009 field measures on Newnes Plateau, near Lithgow, and a seed germination trial are provided. Its survival strategy appears to be that of a stress-tolerator with long-term persistence at (relatively few) suitable sites, and it remains a relatively rare plant. It is conjectured that it is likely to have been a species of greater abundance in the drier, colder and generally treeless conditions of the Newnes Plateau 15–20 000 years ago, but, as conditions became warmer and wetter it has become reduced to isolated populations as taller shrubs outcompeted it for light.
Ob eine Suche nach Rechtsbegriffen des Mittelalters förderlich sei, erscheine – so Harald Siems – zweifelhaft. Theoretische Reflexionen über Recht habe man im Frühen Mittelalter kaum angestellt. Jedenfalls nicht in der Intensität, dass sie sich zum Begriff verdichtet hätten. Die Frage nach dem Rechtsbegriff sei auch deshalb fehl am Platze, weil im Frühmittelalter so etwas zur Lösung von Rechtsfragen nichts hätte beitragen können. Warum sollte jemand auf die Idee kommen, "quasi auf Vorrat" Rechtsbegriffe zu entwickeln? Schon wenn es um konkrete Rechtsfragen wie beispielsweise die Behandlung von Diebstahl oder Raub geht, fehle es "noch lange an Begriff und System". Diese knappe Feststellung bringt Siems’ Ausführungen für einen kurzen Moment in die Nähe von Überlegungen, die Pilch anstellt und die auf dieser Tagung zu verfolgen sind. Aber wirklich nur für einen Augenblick blitzt das auf: Siems sagt, Rechtsbegriffe seien eine schwierige, abstrakte Kategorie, für die heute die Vertreter der Rechtstheorie und der Rechtsphilosophie zuständig seien. ...
Martin Pilchs rechtstheoretische Auseinandersetzung mit dem Begriff der Rechtsgewohnheit bzw. Rechtsgewohnheiten sowie dem Rechtsbegriff als solchem, wie sie seit geraumer Zeit innerhalb der Rechtsgeschichte des Mittelalters diskutiert werden, bietet Gelegenheit zu einer Stellungnahme aus der Perspektive der altorientalischen Rechtsgeschichte. Während in anderen Bereichen der antiken Rechtsgeschichte Rechtsgewohnheiten als Begriff und als Phänomen jedenfalls in jüngerer Zeit durchaus thematisiert werden, spielt dies im Zusammenhang mit Untersuchungen zu den Keilschriftrechten bislang eine allenfalls untergeordnete Rolle. ...
Diese Bemerkungen entspringen einem Diskussionsbeitrag in der lebendigen Januar-Runde. Naturgemäß fehlen etliche Kontexte. Ein Wort auch hier sei trotzdem gewagt, da im Ganzen sonst doch manches beiseite bliebe. Im Hinblick auf hier die gebotene Kürze bitte ich um Verständnis für einige Hinweise auf frühere Ausführungen. ...
IN THE PAST YEARS THE CUSTOMER FEEDBACK METRIC RECOMMENDATION INTENTION HAS GAINED IMPORTANCE, ESPECIALLY DUE TO THE WIDESPREAD CONCEPT NET PROMOTER SCORE (NPS). THE NPS CONCEPT IMPLIES A POSITIVE, NON-LINEAR RELATIONSHIP BETWEEN RECOMMENDATION INTENTION AND CUSTOMER VALUE. THIS ARTICLE INVESTIGATES THE RELATIONSHIP BETWEEN RECOMMENDATION INTENTION OF INDIVIDUAL CUSTOMERS AND THEIR VALUE FOR THE FIRM. THE RESULTS SHOW THAT RECOMMENDATION INTENTION SIGNIFICANTLY INCREASES CONTRIBUTION MARGIN BUT NEITHER RETENTION NOR CUSTOMER VALUE. THE METRIC SATISFACTION HAS A SIGNIFICANT, POSITIVE IMPACT ON CUSTOMER VALUE AND CAN THUS BE USED AS A LEADING INDICATOR. THEREFORE, THE RESULTS DO NOT CONFIRM THE SUPERIORITY OF THE NPS CONCEPT FOR CUSTOMER MANAGEMENT.
Reconhecimento e trabalho em Axel Honneth: os trabalhadores offshore na Bacia de Campos – Brasil
(2010)
Honneth traz ao debate o Hegel dos tempos de Jena e retoma o tema da luta por reconhecimento. Mais recentemente, relê Durkheim que, oitenta anos depois de Hegel, insiste numa nova forma de economia indissociada da eticidade. Propõe que o capitalismo, além da perseguição de metas de eficiência econômica, haverá de se remodelar a partir de critérios normativos que o assegurem como força de integração social. Honneth elege experiências de sofrimento no trabalho como evidências de que a indignação é capaz de ativar lutas por reconhecimento que podem ou não ser articuladas politicamente. A pesquisa elege os trabalhadores offshore no Brasil e demonstra o quanto um setor econômico de ponta também promove entre seus trabalhadores assimetrias de reconhecimento, sobretudo quando as metas produtivas antagonizam-se às demandas por dignidade.
Contrariamente à percepção cotidiana de que os atores estatais têm como objetivo de suas ações o respeito e o reconhecimento da comunidade por eles representada, prevalece na moderna teoria predominante das relações internacionais a noção de que os governos nacionais orientam seu agir essencialmente a fins e não com base em princípios morais. O texto destaca as razões que falam a favor de uma maior consideração da dimensão do reconhecimento na explicação das relações internacionais e explora as implicações normativas que surgem a partir de tal mudança de paradigma para a compreensão e o tratamento das relações internacionais. Narrativas justificadoras da ação política recebem aqui um papel destacado
In contrast to the previous structure determinations of the title structure, (NH4)2[MoS4], the present determination at 173 K localized the positions of the H atoms. The title structure belongs to the beta-K2SO4 family and all the ions are located on crystallographic mirror planes. The ions are held together by N—H ... S hydrogen bonds (some of which are bifurcated), forming a three-dimensional network. One of the N atoms has nine contacts to the S atoms shorter than 4 Å, and the other has ten.
Redewendung
(2010)
Redistribuição versus reconhecimento: apontamentos sobre o debate entre Nancy Fraser e Axel Honneth
(2010)
Resumo: O reconhecimento é uma categoria que tem se revelado muito utilizada para realizar o debate sobre a questão da identidade e da diferença, de modo que sua relevância torna-se incontestável em vários domínios. Sem tecer comentários críticos, o presente texto pretende apresentar o debate travado entre Nancy Fraser e Axel Honneth, referente à preocupação, presente nos dois autores, de se ajustar às pautas de reconhecimento e de distribuição material.
Redistribuição versus reconhecimento: apontamentos sobre o debate entre Nancy Fraser e Axel Honneth
(2010)
O reconhecimento é uma categoria muito utilizada para debater sobre a questão da identidade e da diferença, de modo que sua relevância torna-se incontestável em vários domínios. Sem tecer comentários críticos, o presente texto pretende apresentar o debate travado entre Nancy Fraser e Axel Honneth, referente à preocupação, manifestada pelos dois autores, de se ajustar às pautas de reconhecimento e de distribuição material.
Erich Fromm foi um psicanalista que participou da formação da Escola de Frankfurt com o projeto de unir o materialismo histórico de Marx à psicanálise de Freud. Dentre os conceitos abordados por ele, o da liberdade é um dos fundamentais, ao postular a diferença entre a “liberdade de” e a “liberdade para”, sendo a primeira a liberdade existente na sociedade capitalista, uma pseudo-liberdade, e a segunda seria a realização da liberdade no sentido positivo. Contudo, devido ao seu humanismo abstrato e não perceber o papel da luta de classes no sentido da superação do capitalismo, elabora uma crítica contundente dessa sociedade, que, no entanto, se torna limitada.
Reificação e reconhecimento: um estudo a partir da teoria crítica da sociedade de Axel Honneth
(2010)
O conceito de reificação, originalmente formulado por Karl Marx e desenvolvido por Georg Lukács, foi incorporado como uma das categorias centrais da teoria crítica em sua tarefa de diagnosticar patologias sociais. Contudo, para a compreensão atual da utilização do conceito, tornou-se necessário libertar seu referencial originário meramente econômico. É isso o que pretende Axel Honneth ao reatualizar o conceito de reificação e seu potencial crítico-normativo a partir da teoria do reconhecimento. Além de retomar os principais aspectos do conceito de reificação segundo a análise do “fetichismo da mercadoria”, o artigo se concentra em apresentar a interpretação de Honneth para os processos sociais reificantes – nas relações dos sujeitos com o mundo circundante, nas relações sociais entre os sujeitos e nos efeitos patológicos da autoreificação sobre a autorealização ética – e para a produção inovadora do diagnóstico das patologias sociais decorrentes da reificação como “esquecimento do reconhecimento”.