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Abstract: Fine-scale temporal organization of cortical activity in the gamma range (∼25–80Hz) may play a significant role in information processing, for example by neural grouping ('binding') and phase coding. Recent experimental studies have shown that the precise frequency of gamma oscillations varies with input drive (e.g. visual contrast) and that it can differ among nearby cortical locations. This has challenged theories assuming widespread gamma synchronization at a fixed common frequency. In the present study, we investigated which principles govern gamma synchronization in the presence of input-dependent frequency modulations and whether they are detrimental for meaningful input-dependent gamma-mediated temporal organization. To this aim, we constructed a biophysically realistic excitatory-inhibitory network able to express different oscillation frequencies at nearby spatial locations. Similarly to cortical networks, the model was topographically organized with spatially local connectivity and spatially-varying input drive. We analyzed gamma synchronization with respect to phase-locking, phase-relations and frequency differences, and quantified the stimulus-related information represented by gamma phase and frequency. By stepwise simplification of our models, we found that the gamma-mediated temporal organization could be reduced to basic synchronization principles of weakly coupled oscillators, where input drive determines the intrinsic (natural) frequency of oscillators. The gamma phase-locking, the precise phase relation and the emergent (measurable) frequencies were determined by two principal factors: the detuning (intrinsic frequency difference, i.e. local input difference) and the coupling strength. In addition to frequency coding, gamma phase contained complementary stimulus information. Crucially, the phase code reflected input differences, but not the absolute input level. This property of relative input-to-phase conversion, contrasting with latency codes or slower oscillation phase codes, may resolve conflicting experimental observations on gamma phase coding. Our modeling results offer clear testable experimental predictions. We conclude that input-dependency of gamma frequencies could be essential rather than detrimental for meaningful gamma-mediated temporal organization of cortical activity.
Author Summary: Almost 350 years ago the physicist and polymath Christiaan Huygens first observed the synchronization between two pendulum clocks attached to a common support. Since then synchronization has been recognized as a universal phenomenon from astronomy to biology. The phase-locking (synchrony) and the phase-relation between the two pendulums are determined by two principal forces: the synchronization force exerted over the connection and the tendency to desynchronize due to frequency (speed) differences. We propose that gamma synchronization (25–80Hz) among oscillating cortical neurons in the brain can be understood according to the same principles—like a field of many connected pendula—with the critical addition that input changes the frequency of gamma oscillations, as shown by recent experimental studies. It has been assumed that input-dependent changes in oscillation frequency are detrimental for a meaningful role of gamma synchronization in neural processing. To the contrary, our theoretical analysis demonstrates that because input can change the frequency of the oscillation, phase-locking and phase-relations among neurons relate systematically to input. By analogy, it is because a local push to a pendulum will change its frequency, that resulting changes in phase-locking and phase-relation among the pendula can be used to derive the external force applied.
What happened to the tremendous legacy of juridical knowledge left behind in Italy in the 6th century? Into what labyrinth did it plunge only to re-emerge after the silent age of the early Middle Ages into the light of day, and effectively come to shape the renewal of the jurisprudence at the beginning of the 12th century? One-and-a-half centuries after the fanciful writings of Hermann Fitting, legal historians are still looking for the answers to these questions. Considering the new information we have (especially coming from the paleographical research), this paper re-examines the existence as well as the activities of the school of Rome both during the Justinian Age and in the two centuries thereafter. The aim of this essay is to verify whether Rome, during the very early Middle Ages, continued to represent a centre of juridical culture. According to the hypothesis developed in this contribution, Rome – at that time – not only played a very important role with regard to the material conservation of the Justinian’s libri legales, but also in the initial establishment of the new (i. e., Justinian) imperial law in the West and creation of its image as a significant juridical centre. The absence of such a centre as well as its wide-spread image would truly make the Bolognese renovatio appear "miraculous" and very difficult to explain.
After Justinian, the 7th and 8th centuries can truly be characterised as "silent" in the history of Roman law in the West. However, by studying the medieval manuscript tradition, in particular, that of the Institutiones and the Novellae, we can gather together a series of elements helping us to clarify the situation. Also quite useful is an examination of the manuscript tradition of the Collatio legum Mosaicarum et Romanarum. Through the spread and use of these Late Antique works, we can see how – in conjunction with the actions of the papacy – Rome, toward the end of the 8th century, returned to being a centre of world politics and – given that law follows politics – of the legal culture.
WE DECOMPOSE INDIVIDUAL INVESTORS’ PORTFOLIO RETURNS INTO PASSIVE BENCHMARK RETURNS, ACTIVE SECURITY SELECTION RETURNS, AND ACTIVE MARKET TIMING RETURNS. FOR THE AVERAGE INVESTOR IN OUR SAMPLE, PASSIVE BENCHMARK RETURNS EXPLAIN SOME 40% OF VARIATION IN LONGITUDINAL PORTFOLIO RETURNS, SECURITY SELECTION EXPLAINS AN ADDITIONAL 50%, AND MARKET TIMING PLAYS ONLY A MINOR ROLE. THIS STANDS IN STARK CONTRAST TO EARLIER RESULTS ON INSTITUTIONAL INVESTORS WHERE PASSIVE BENCHMARK RETURNS (REFLECTING DIFFERENT ASSET ALLOCATION STRATEGIES) EXPLAIN OVER 90%. THE PREDOMINANCE OF SECURITY SELECTION COMES AT A COST FOR INDIVIDUAL INVESTORS: INVESTORS FROM THE HIGHEST QUINTILE IN TERMS OF SECURITY SELECTION ACTIVITY UNDERPERFORM THEIR PEERS FROM THE LOWEST QUINTILE BY MORE THAN 10 PERCENTAGE POINTS PER YEAR. TRANSACTION COSTS EXPLAIN ONLY PART OF THIS UNDERPERFORMANCE. THE LESS INVESTORS DIVERSIFY, THE WORSE THEY DO.
In diesem Jahr hat sich die Paul Ehrlich-Stiftung für zwei Preisträger entschieden, die sich den mit 100.000 Euro dotierten Paul Ehrlich- und Ludwig Darmstaedter-Preis teilen. Am 14.03.2015 überreichte Professor Harald zur Hausen, der Vorsitzende des Stiftungsrates, in der Frankfurter Paulskirche den Preis an Professor James P. Allison vom MD Anderson Cancer Center in Houston (Foto Mitte) und an Professor Carl H. June von der Universität Pennsylvania in Philadelphia (r.). Professor Raja Atreya vom Universitätsklinikum in Erlangen (l.) erhielt den Paul Ehrlich- und Ludwig Darmstaedter-Nachwuchspreis.
Background: The objective measurement of the mechanical component and its role in chronic ankle instability is still a matter of scientific debate. We analyzed known group and diagnostic validity of our ankle arthrometer. Additionally, functional aspects of chronic ankle instability were evaluated in relation to anterior talar drawer.
Methods: By manual stress testing, 41 functionally unstable ankles were divided as mechanically stable (n = 15) or mechanically unstable (n = 26). Ankle laxity was quantified using an ankle arthrometer. Stiffness values from the load displacement curves were calculated between 40 and 60 N. Known group validity and eta2 were established by comparing manual and arthrometer testing results. Diagnostic validity for the ankle arthrometer was determined by a 2 × 2 contingency table. The functional ankle instability severity was quantified by the German version of the Foot and Ankle Ability Measure (FAAM-G). Stiffness (40–60 N) and FAAM-G values were correlated.
Results: Mechanically unstable ankles had lower 40–60 N stiffness values than mechanically stable ankles (p = 0.006 and <0.001). Eta for the relation between manual and arthrometer anterior talar drawer testing was 0.628. With 5.1 N/mm as cut-off value, accuracy, sensitivity, and specificity were 85%, 81%, and 93%, respectively. The correlation between individual 40–60 N arthrometer stiffness values and FAAM-G scores was r = 0.286 and 0.316 (p = 0.07 and 0.04).
Conclusions: In this investigation, the ankle arthrometer demonstrated a high diagnostic validity for the determination of mechanical ankle instability. A clear interaction between mechanical (ankle arthrometer) and functional (FAAM-G) measures could not be demonstrated.
Dies ist der zehnte Artikel unseres Blogfokus „Salafismus in Deutschland“.
Was macht salafistisches Denken in religiöser Hinsicht aus? Was hat Salafismus mit Wahhabismus zu tun? Was hat Dschihadismus mit Salafismus zu tun? Alles Fragen, auf die es keine einfachen Antworten gibt. Trotzdem lohnt der Versuch, eine Antwort zu geben, da die religiösen Vorstellungen zentral für die Identität des Salafismus sind. Es geht hier „nur“ um die religiösen Ideen, die immer wieder in salafistischen Diskussionen auftreten. Freilich ist die innersalafistische Debatte vielgestaltig, so dass sich kein „Katechismus“ aufstellen lässt, der ausweist, woran ein/e SalafistIn glaubt. Deshalb werden im Folgenden entlang einzelner Stränge des salafistischen Diskurses ausgewählte religiöse Ideen beleuchtet....
n the EU there are longstanding and ongoing pressures towards a tax that is levied on the EU level to substitute for national contributions. We discuss conditions under which such a transition can make sense, starting from what we call a "decentralization theorem of taxation" that is analogous to Oates (1972) famous result that in the absence of spill-over effects and economies of scale decentralized public good provision weakly dominates central provision. We then drop assumptions that turn out to be unnecessary for this results. While spill-over effects of taxation may call for central rules for taxation, as long as spill-over effects do not depend on the intra-regional distribution of the tax burden, decentralized taxation plus tax coordination is found superior to a union-wide tax.
Background. Bile leakage testing may help to detect and reduce the incidence of biliary leakage after hepatic resection. This review was performed to investigate the value of the White-test in identifying intraoperative biliary leakage and avoiding postoperative leakage.
Material and methods. A systematic review and meta-analysis was performed. Two researchers performed literature research. Primary outcome measure was the incidence of post-hepatectomy biliary leakage; secondary outcome measure was the ability of detecting intraoperative biliary leakage with the help of the White-test.
Results. A total of 4 publications (including original data from our center) were included in the analysis. Evidence levels of the included studies had medium quality of 2b (individual cohort studies including low quality randomized controlled trials). Use of the White-test led to a significant reduction of post-operative biliary leakage [OR: 0.3 (95% CI: 0.14, 0.63), p = 0.002] and led to a significant higher intraoperative detection of biliary leakages [OR: 0.03 (95%CI: 0.02, 0.07), p < 0.00001].
Conclusion. Existing evidence implicates the use of the White-test after hepatic resection to identify bile leaks intraoperatively and thus reduce incidence of post-operative biliary leakage. Nonetheless, there is a requirement for a high-quality randomized controlled trial with adequately powered sample-size to confirm findings from the above described studies and further increase evidence in this field.
Second mitochondria-derived activator of caspase (Smac) mimetics are considered as promising anticancer therapeutics that are currently under investigation in early clinical trials. They induce apoptosis by antagonizing inhibitor of apoptosis proteins, which are frequently overexpressed in cancer. We previously reported that Smac mimetics, such as BV6, additionally exert non-apoptotic functions in glioblastoma (GBM) cells by stimulating migration and invasion in a nuclear factor kappa B (NF-κB)-dependent manner. Because NF-κB target genes mediating these effects are largely unknown, we performed whole-genome expression analyses. Here, we identify chemokine (C-C motif) ligand 2 (CCL2) as the top-listed NF-κB-regulated gene being upregulated upon BV6 treatment in GBM cells. BV6-induced upregulation and secretion of CCL2 are required for migration and invasion of GBM cells because knockdown of CCL2 in GBM cells abolishes these effects. Co-culture experiments of GBM cells with non-malignant astroglial cells reveal that BV6-stimulated secretion of CCL2 by GBM cells into the supernatant triggers migration of astroglial cells toward GBM cells because CCL2 knockdown in BV6-treated GBM cells impedes BV6-stimulated migration of astroglial cells. In conclusion, we identify CCL2 as a BV6-induced NF-κB target gene that triggers migration and invasion of GBM cells and exerts paracrine effects on the GBM's microenvironment by stimulating migration of astroglial cells. These findings provide novel insights into the biological functions of Smac mimetics with important implications for the development of Smac mimetics as cancer therapeutics.
Wasserbedarfsprognosen sind für Wasserversorger eine wichtige Entscheidungsgrundlage für zukünftige Maßnahmen in der wirtschaftlichen und technischen Betriebsführung sowie beim Ressourcenmanagement. In den letzten zwei Jahrzehnten sanken in Deutschland die spezifischen Wasserbedarfe aufgrund von Technik- und Verhaltensinnovationen. Für Regionen mit Wirtschafts- und Bevölkerungswachstum ist aber das Zusammenspiel dieser für den zukünftigen Bedarf konträren Entwicklungen von besonderem Interesse. Auch die Metropolregion Hamburg ist von diesen Entwicklungen betroffen.
Im Auftrag des Wasserversorgers HAMBURG WASSER aktualisierte das ISOE (Forschungsschwerpunkt Wasserressourcen und Landnutzung) in Kooperation mit dem ifo Institut München seine mittel- und langfristige Wasserbedarfsprognose aus dem Jahr 2007 für das Versorgungsgebiet des Auftraggebers. In einem innovativen Konzept wurden dafür Forschungsmethoden aus Natur-, Wirtschafts-, Planungs- und Sozialwissenschaften kombiniert. Mit dem gewählten transdisziplinären Forschungsmodus war das Projekt darauf angelegt, im laufenden Forschungsprozess gemeinsam mit den wissenschaftlichen und außerwissenschaftlichen Projektpartnern das Prognosekonzept weiterzuentwickeln. Der vorliegende Studientext basiert auf dem Projektbericht an HAMBURG WASSER und fasst Prognosekonzept, Modellentwicklung, Prognoseergebnissen und Schlussfolgerungen zusammen.
Rain- and floodwater harvesting (RFWH) technologies and water reuse are ideal and generalpurpose technologies to improve water security and to contribute to climate adaptation – in particular for semi-arid regions. These technologies are part of a multi-resources mix within an integrated water resources management (IWRM). They create capacities to buffer water fluctuations and alleviate water scarcity. In this way, they reduce the pressure on existing resources, and can stimulate local economies. However, in order to be sustainable, these technologies need to be adapted to the local context – through suitable design, adapted operation requirements, and a back-up by training users and operators accordingly.
Background: The introduction of modern troponin assays has facilitated diagnosis of acute myocardial infarction due to improved sensitivity with corresponding loss of specificity. Atrial fibrillation (AF) is associated with elevated levels of troponin. The aim of the present study was to evaluate the diagnostic performance of troponin I in patients with suspected acute coronary syndrome and chronic AF.
Methods: Contemporary sensitive troponin I was assayed in a derivation cohort of 90 patients with suspected acute coronary syndrome and chronic AF to establish diagnostic cut-offs. These thresholds were validated in an independent cohort of 314 patients with suspected myocardial infarction and AF upon presentation. Additionally, changes in troponin I concentration within 3 hours were used.
Results: In the derivation cohort, optimized thresholds with respect to a rule-out strategy with high sensitivity and a rule-in strategy with high specificity were established. In the validation cohort, application of the rule-out cut-off led to a negative predictive value of 97 %. The rule-in cut-off was associated with a positive predictive value of 88 % compared with 71 % if using the 99th percentile cut-off. In patients with troponin I levels above the specificity-optimized threshold, additional use of the 3-hour change in absolute/relative concentration resulted in a further improved positive predictive value of 96 %/100 %.
Conclusions: Troponin I concentration and the 3-hour change in its concentration provide valid diagnostic information in patients with suspected myocardial infarction and chronic AF. With regard to AF-associated elevation of troponin levels, application of diagnostic cut-offs other than the 99th percentile might be beneficial.
Patienten mit einer BCR/ABL positiven (Ph+) akuten lymphatischen Leukämie (ALL) bilden die größte genetisch definierte Untergruppe der ALL und gelten wegen ihrer schlechten Prognose als Höchstrisiko ALL. Die bisherigen Therapieergebnisse werden durch die Kombination von Tyrosin-Kinase-Inhibitoren (TKI) wie Imatinib und Chemotherapeutika verbessert, sind aber durch das Auftreten von Resistenzen gegen TKI in ihrer langfristigen Wirkung limitiert. Die derzeitige Forschung fokussiert sich weitestgehend auf konstitutive aktive Kinasen, die für die leukämische Transformation verantwortlich sind. Allerdings kann die Deregulation von Phosphatasen, die als Gegenspieler von Kinasen fungieren, durch eine verminderte Inaktivierung dieser Kinasen, ebenso zur Leukämogenese beitragen, indem ihre physiologische Funktion vermindert wird. Im Vorfeld konnte bereits gezeigt werden, dass die deregulierte Protein Tyrosin Phosphatase 1B (PTP1B) bei Ph+ Leukämien eine partielle Resistenz gegenüber TKI vermitteln kann.1 Darüber hinaus zeigen von Juric et al. (2007)2 publizierte Microarrays von 54 Ph+ ALL Patienten eine transkriptionelle Hochregulierung der Phosphatase „Supressor of T-Cell receptor Signalling 1“ (STS-1).2 STS-1 (TULA-2) gehört zusammen mit STS-2 (TULA-1) zur Familie der STS/TULA Proteine, von denen keine weiteren Mitglieder bekannt sind. STS-1 dephosphoryliert diverse Rezeptor-Tyrosin-Kinasen wie z.B. den T-Cell Receptor (TCR) und den Epidermal-Growth-Factor Receptor (EGFR) und verhindert somit deren Internalisierung und proteosomalen Abbau.3 Weitere durch STS-1 dephosphorylierte Substrate sind die Proteintyrosinkinase Syk, die eine wichtige Rolle bei der Signalweiterleitung des B-Cell-Receptors (BCR) spielt sowie andere SRC-Kinasen (z.B. FYN).4 Aufgrund der oben beschriebenen Zusammenhänge zwischen STS-1 und der Ph+ ALL ist die Untersuchung einer möglichen funktionellen Bedeutung von STS-1 bei der Entwicklung einer mutationsunabhängigen Resistenz von Ph+ ALL Inhalt dieser Arbeit. Als Modellsystem dienen in der hier vorliegenden Arbeit aus der BCR/ABL Zelllinie Sup B15 abgeleitete TKI resistente Zellen (Sup B15 RT). Imatinib ist in diesen immer noch in der Lage BCR/ABL zu binden und führt zu einer Verschiebung der Dosiswirkungskurve ohne Apoptose zu induzieren. Mutationen in der Tyrosinkinase Domäne von BCR/ABL konnten als zugrunde liegender Resistenzmechanismus durch Sequenzanalysen ausgeschlossen werden, ebenso wie zusätzliche Translokationen oder genomischen Amplifikationen von BCR/ABL. Eine Analyse der STS-1 Expression zeigte sowohl transkriptionell als auch auf Proteinebene eine deutliche Herunterregulierung von STS-1 in Sup B15 RT Zellen. Die Interaktion zwischen STS-1 und BCR/ABL wurde in verschiedenen Zellmodellen gezeigt. Dabei konnten bezüglich der Interaktion keine Unterschiede zwischen dem p210BCR/ABL und p185BCR/ABL Fusionsprotein festgestellt werden. Auch die „Gatekeeper“ Mutation T315I hatte keinen Einfluss auf die Interaktion. Die Unabhängigkeit der Bindung von STS-1 und BCR/ABL von einer aktiven BCR/ABL Kinase wurde durch die Zugabe von Imatinib gezeigt. Lediglich auf endogenem Level konnte eine Imatinib vermittelte Reduktion der Interaktion nachgewiesen werden. Durch die Verwendung unterschiedlich trunkierter BCR/ABL Proteine wurde gezeigt, dass STS-1 sowohl mit c-ABL als auch mit dem ABL-Anteil von BCR/ABL interagiert und dass eine Oligomerisierung für diese Interaktion nicht notwendig ist. Als Folge der Interaktion kommt es zu einer Dephosphorylierung von BCR/ABL durch STS-1, wobei vor allem die im ABL Anteil lokalisierten und für die Autophosphorylierung wichtigen Tyrosine 245 und 412 dephosphoryliert werden. Mittels eines Proliferations-Kompetitions-Assay konnte gezeigt werden, dass STS-1 sowohl die Proliferationsrate reduziert als auch erheblich die Sensitivität von SupB15 RT Zellen gegenüber Imatinib steigert. Dieser Befund steht im Einklang mit der Annahme, dass diese Sensitivitätssteigerung durch eine gegenüber den sensitiven Sup B15 WT deutlich verminderte STS-1 Expression bedingt ist. Dexamethason in klinisch relevanten Konzentrationen (10-6 M - 10-9 M) konnte sowohl in SupB15 WT als auch in SupB15 RT Zellen die STS-1 Expression um ein Vielfaches steigern und führte in Kombination mit 1 μM Imatinib sogar in den resistenten Zellen zu einer hoch signifikanten Inhibition der Proliferation sowie einer gesteigerten Apoptose. Die Resultate dieser Arbeit rücken Phosphatasen und im speziellen STS-1 in einen stärkeren Fokus, wenn es um die Bildung von Resistenzen geht. Dadurch können sich eine Vielzahl neuer Behandlungsstrategien sowie neue Ansätze für die klinische Wirkstoffforschung ergeben.
This paper investigates the effect of a change in informational environment of borrowers on the organizational design of bank lending. We use micro-data from a large multinational bank and exploit the sudden introduction of a credit registry, an information-sharing mechanism across banks, for a subset of borrowers. Using within borrower and loan officer variation in a difference-in-difference empirical design, we show that expansion of credit registry led to an improvement in allocation of credit to affected
borrowers. There was a concurrent change in the organizational structure of the bank that involved a dramatic increase in delegation of lending decisions of affected borrowers to loan officers. We also find a significant expansion in scope of activities of loan officers who deal primarily with affected borrowers, as well as of their superiors. There is suggestive evidence that larger banks in the economy were better able to implement similar changes as our bank. We argue that these patterns can be understood within the framework of incentive-based and information cost processing theories. Our findings could help rationalize why improvements in the information environment of borrowers may be altering the landscape of lending by moving decisions outside the boundaries of financial intermediaries.
Unusual Deep Water sponge assemblage in South China - witness of the end-Ordovician mass extinction
(2015)
There are few sponges known from the end-Ordovician to early-Silurian strata all over the world, and no records of sponge fossils have been found yet in China during this interval. Here we report a unique sponge assemblage spanning the interval of the end-Ordovician mass extinction from the Kaochiapien Formation (Upper Ordovician-Lower Silurian) in South China. This assemblage contains a variety of well-preserved siliceous sponges, including both Burgess Shale-type and modern type taxa. It is clear that this assemblage developed in deep water, low energy ecosystem with less competitors and more vacant niches. Its explosion may be related to the euxinic and anoxic condition as well as the noticeable transgression during the end-Ordovician mass extinction. The excellent preservation of this assemblage is probably due to the rapid burial by mud turbidites. This unusual sponge assemblage provides a link between the Burgess Shale-type deep water sponges and the modern forms. It gives an excellent insight into the deep sea palaeoecology and the macroevolution of Phanerozoic sponges, and opens a new window to investigate the marine ecosystem before and after the end-Ordovician mass extinction. It also offers potential to search for exceptional fossil biota across the Ordovician-Silurian boundary interval in China.
Understanding how to achieve efficient transduction of hematopoietic stem and progenitor cells (HSPCs), while preserving their long-term ability to self-reproduce, is key for applying lentiviral-based gene engineering methods. SAMHD1 is an HIV-1 restriction factor in myeloid and resting CD4+ T cells that interferes with reverse transcription by decreasing the nucleotide pools or by its RNase activity. Here we show that SAMHD1 is expressed at high levels in HSPCs cultured in a medium enriched with cytokines. Thus, we hypothesized that degrading SAMHD1 in HSPCs would result in more efficient lentiviral transduction rates. We used viral like particles (VLPs) containing Vpx, shRNA against SAMHD1, or provided an excess of dNTPs or dNs to study this question. Regardless of the method applied, we saw no increase in the lentiviral transduction rate. The result was different when we used viruses (HR-GFP-Vpx+) which carry Vpx and encode GFP. These viruses allow assessment of the effects of Vpx specifically in the transduced cells. Using HR-GFP-Vpx+ viruses, we observed a modest but significant increase in the transduction efficiency. These data suggest that SAMHD1 has some limited efficacy in blocking reverse transcription but the major barrier for efficient lentiviral transduction occurs before reverse transcription.
Wild plant species are important nutritious supplements to otherwise nutrient poor diets of rural populations in West Africa. Consequently, a decline of wild food species has a direct negative impact on the nutritional status of local households. In this study, we firstly investigated the preferred wild food species in south-east Burkina Faso, their perceived change in abundance as well as their contribution to wild food income. Secondly, we studied how these species might be substituted in times of species shortfall. Thirdly, we investigated the impact of socio-economic variables on the substitution choice. We conducted 155 household interviews in two villages and found 21 wild food species. With a contribution of almost 70% to wild food income, Vitellaria paradoxa and Parkia biglobosa were economically most important. All species were considered declining to some degree. The wide range of cited substitutes for the ten most important wild food species indicates a great knowledge on alternative plant species in the area. For the majority, the substitution choice did not depend on socio-economic characteristics. Cited as surrogate for several important wild food species, the native tree Balanites aegyptiaca was the most important substitute species. Many valued wild food species were substituted with other highly valued wild food species and therefore the decline of one species can lead to a shortfall of another substitute. Thus, even though our results suggest that people are able to counteract the decrease or absence of wild food species, growing decline of one species would concurrently increase the pressure on other native food species.
Rpn13 is an intrinsic ubiquitin receptor of the 26S proteasome regulatory subunit that facilitates substrate capture prior to degradation. Here we show that the C-terminal region of Rpn13 binds to the tetratricopeptide repeat (TPR) domain of SGTA, a cytosolic factor implicated in the quality control of mislocalised membrane proteins (MLPs). The overexpression of SGTA results in a substantial increase in steady-state MLP levels, consistent with an effect on proteasomal degradation. However, this effect is strongly dependent upon the interaction of SGTA with the proteasomal component Rpn13. Hence, overexpression of the SGTA-binding region of Rpn13 or point mutations within the SGTA TPR domain both inhibit SGTA binding to the proteasome and substantially reduce MLP levels. These findings suggest that SGTA can regulate the access of MLPs to the proteolytic core of the proteasome, implying that a protein quality control cycle that involves SGTA and the BAG6 complex can operate at the 19S regulatory particle. We speculate that the binding of SGTA to Rpn13 enables specific polypeptides to escape proteasomal degradation and/or selectively modulates substrate degradation.
Der Jahrgang 2014 des Masterstudiengangs Curatorial Studies wurde von der KW Institute for Contemporary Art in Berlin eingeladen, eine Ausstellungsserie für den kleinen Raum »3 ½« zu konzipieren und eigenständig durchzuführen. Inhaltliche Vorgaben gab es dafür keine. Eine große Chance, aber auch eine Herausforderung, schließlich haben alle verschiedene Vorstellungen davon, was eine Ausstellung ausmacht.
Background: Lithium has proven suicide preventing effects in the long-term treatment of patients with affective disorders. Clinical evidence from case reports indicate that this effect may occur early on at the beginning of lithium treatment. The impact of lithium treatment on acute suicidal thoughts and/or behavior has not been systematically studied in a controlled trial. The primary objective of this confirmatory study is to determine the association between lithium therapy and acute suicidal ideation and/or suicidal behavior in inpatients with a major depressive episode (MDE, unipolar and bipolar disorder according to DSM IV criteria). The specific aim is to test the hypothesis that lithium plus treatment as usual (TAU), compared to placebo plus TAU, results in a significantly greater decrease in suicidal ideation and/or behavior over 5 weeks in inpatients with MDE.
Methods/Design: We initiated a randomized, placebo-controlled multicenter trial. Patients with the diagnosis of a moderate to severe depressive episode and suicidal thoughts and/or suicidal behavior measured with the Sheehan-Suicidality-Tracking Scale (S-STS) will be randomly allocated to add lithium or placebo to their treatment as usual. Change in the clinician administered S-STS from the initial to the final visit will be the primary outcome.
Discussion: There is an urgent need to identify treatments that will acutely decrease suicidal ideation and/or suicidal behavior. The results of this study will demonstrate whether lithium reduces suicidal ideation and behavior within the first 5 weeks of treatment.
Intrinsic covariation of brain activity has been studied across many levels of brain organization. Between visual areas, neuronal activity covaries primarily among portions with similar retinotopic selectivity. We hypothesized that spontaneous inter-areal co-activation is subserved by neuronal synchronization. We performed simultaneous high-density electrocorticographic recordings across several visual areas in awake monkeys to investigate spatial patterns of local and inter-areal synchronization. We show that stimulation-induced patterns of inter-areal co-activation were reactivated in the absence of stimulation. Reactivation occurred through both, inter-areal co-fluctuation of local activity and inter-areal phase synchronization. Furthermore, the trial-by-trial covariance of the induced responses recapitulated the pattern of inter-areal coupling observed during stimulation, i.e. the signal correlation. Reactivation-related synchronization showed distinct peaks in the theta, alpha and gamma frequency bands. During passive states, this rhythmic reactivation was augmented by specific patterns of arrhythmic correspondence. These results suggest that networks of intrinsic covariation observed at multiple levels and with several recording techniques are related to synchronization and that behavioral state may affect the structure of intrinsic dynamics.
Als sich am 16. Mai 1891 die Drehkreuze zur Internationalen Elektrotechnischen Ausstellung vor dem Frankfurter Bahnhof öffneten, gab es unter den Besuchern kaum noch Zweifel: Elektrizität und künstliche Helligkeit werden die westliche Zivilisation und ihre urbanen Lebenswelten geradezu revolutionär verändern. Das sollte sich bewahrheiten!
In der ersten Netzschau im Neuen Jahr geht es um das (vermeintliche) Aussterben des Folterverbots in den USA, Drohnen in Europa, Demokratisierungstrends in den kommenden zehn Jahren, die Finanzierung des UN-Menschenrechtspfeilers und die Konkurrenz zwischen al Qaida und dem Islamischen Staat – auch im Lichte der Anschläge von Paris.
Die AG Internationale Beziehungen der Deutschen Nachwuchsgesellschaft für Politik- und Sozialwissenschaft (DNGPS) hält die Fachtagung 2016 zum Thema “Gesucht: Europäische Außenpolitik” vom 16. bis 18. März 2016 in Trier ab. Alle weiteren Infos findet Ihr im Call for Paper, der sich an Studierende und Promovierende richtet!
Vom 14. bis 15. Januar 2016 findet in Kassel eine Konferenz zum Thema "Beyond the Master's Tools: Post- and Decolonial Approaches to Research Methodology and Methods in the Social Sciences" statt. Veranstaltet wird die Konferenz von den Fachbereichen Postkoloniale Studien und Soziologie der Diversität der Universität Kassel.
Die HBO-Serie The Wire erzählt eine Geschichte von Kriminalität, Polizeiarbeit und Politik in Baltimore. Eine ihrer Stärken liegt darin, wie sie die Ambivalenz des sozialen und politischen Lebens nachzeichnet. Eine zentrale Rolle spielt dabei allgegenwärtige Korruption. Ihre Ambivalenz bricht sich nicht zuletzt in der Darstellung der Figur des State Senator Clay Davis.
Limb loss is a devastating disability and while current treatments provide aesthetic and functional restoration, they are associated with complications and risks. The optimal solution would be to harness the body's regenerative capabilities to regrow new limbs. Several methods have been tried to regrow limbs in mammals, but none have succeeded. One such attempt, in the early 1970s, used electrical stimulation and demonstrated partial limb regeneration. Several researchers reproduced these findings, applying low voltage DC electrical stimulation to the stumps of amputated rat forelimbs reporting "blastema, and new bone, bone marrow, cartilage, nerve, skin, muscle and epiphyseal plate formation". In spite of these encouraging results this research was discontinued. Recently there has been renewed interest in studying electrical stimulation, primarily at a cellular and subcellular level, and studies have demonstrated changes in stem cell behavior with increased proliferation, differentiation, matrix formation and migration, all important in tissue regeneration. We applied electrical stimulation, in vivo, to the stumps of amputated rat limbs and observed significant new bone, cartilage and vessel formation and prevention of neuroma formation. These findings demonstrate that electricity stimulates tissue regeneration and form the basis for further research leading to possible new treatments for regenerating limbs.
Promove-se uma recuperação do debate endógeno estabelecido entre alguns pensadores da Escola de Frankfurt, sobretudo no que se refere às diferentes perspectivas de análise sobre as relações entre ação e estrutura social, bem como as distintas percepções acerca das racionalidades (prática ou comunicativa) que organizam a conexão entre os indivíduos e a sociedade. Verifica-se o modo como os autores ligados à teoria crítica compreenderam as relações entre esferas subjetivas e estruturais em termos de possibilidades de emancipação social e de exercício de práticas deliberativas. Nessa perspectiva, considera-se uma cisão teórica estabelecida no interior da própria escola, cuja expressão se dá a partir das diferenças epistemológicas existentes entre o núcleo central do pensamento frankfurtiano e um conjunto de autores periféricos. Os trabalhos produzidos por esse núcleo “marginal”, bem como seu posterior refinamento na obra de Habermas, apresentam alternativas teóricas de caráter relacional que contrapõem a visão estrutural e cética presente nos trabalhos de Horkheimer, Adorno e Marcuse. É justamente na recuperação dessas fronteiras endógenas que se pretende ponderar as possíveis contribuições do pensamento frankfurtiano para uma perspectiva crítica da sociedade contemporânea.
Although much is known about the critical importance of active verbal rehearsal for successful recall, knowledge about the mechanisms of rehearsal and their respective development in children is very limited. To be able to rehearse several items together, these items have to be available, or, if presented and rehearsed previously, retrieved from memory. Therefore, joint rehearsal of several items may itself be considered recall. Accordingly, by analyzing free recall, one cannot only gain insight into how recall and rehearsal unfold, but also into how principles that govern children’s recall govern children’s rehearsal. Over a period of three and a half years (beginning at grade 3) 54 children were longitudinally assessed seven times on several overt rehearsal free recall trials. A first set of analyses on recall revealed significant age-related increases in the primacy effect and an age-invariant recency effect. In the middle portion of the list, wave-shaped recall characteristics emerged and increased with age, indicating grouping of the list into subsequences. In a second set of analyses, overt rehearsal behavior was decomposed into distinct rehearsal sets. Analyses of these sets revealed that the distribution of rehearsals within each set resembled the serial position curves with one- or two-item primacy and recency effects and wave-shaped rehearsal patterns in between. In addition, rehearsal behavior throughout the list was characterized by a decreasing tendency to begin rehearsal sets with the first list item. This result parallels the phenomenon of beginning recall with the first item on short lists and with the last item on longer lists.
Background: Influenza vaccination is recommended for all healthcare personnel (HCP) and most institutions offer vaccination for free and on site. However, medical students do not always have such easy access, and the predictors that might guide the motivation of medical students to get vaccinated are largely unknown.
Methods: We conducted a cross-sectional survey study among pre-clinical medical students in a German University hospital to assess the social cognitive predictors of influenza vaccination, as well as reasons for refusal and acceptance of the vaccine.
Results: Findings show that pre-clinical medical students have comparable knowledge gaps and negative attitudes towards influenza vaccination that have previously been reported among HCP. Lower injunctive norms and higher feelings of autonomy contribute to no intention to get vaccinated against influenza, while a positive instrumental attitude and higher feelings of autonomy contribute to a high intention to get vaccinated. The variables in the regression model explained 20% of the variance in intention to get vaccinated. Conclusions: The identified factors should be addressed early in medical education, and hospitals might benefit from a more inclusive vaccination program and accessibility of free vaccines for their medical students.
Synesthesia is a phenomenon in which additional perceptual experiences are elicited by sensory stimuli or cognitive concepts. Synesthetes possess a unique type of phenomenal experiences not directly triggered by sensory stimulation. Therefore, for better understanding of consciousness it is relevant to identify the mental and physiological processes that subserve synesthetic experience. In the present work we suggest several reasons why synesthesia has merit for research on consciousness. We first review the research on the dynamic and rapidly growing field of the studies of synesthesia. We particularly draw attention to the role of semantics in synesthesia, which is important for establishing synesthetic associations in the brain. We then propose that the interplay between semantics and sensory input in synesthesia can be helpful for the study of the neural correlates of consciousness, especially when making use of ambiguous stimuli for inducing synesthesia. Finally, synesthesia-related alterations of brain networks and functional connectivity can be of merit for the study of consciousness.
African trypanosomes cause a parasitic disease known as sleeping sickness. Mitochondrial transcript maturation in these organisms requires a RNA editing reaction that is characterized by the insertion and deletion of U-nucleotides into otherwise non-functional mRNAs. Editing represents an ideal target for a parasite-specific therapeutic intervention since the reaction cycle is absent in the infected host. In addition, editing relies on a macromolecular protein complex, the editosome, that only exists in the parasite. Therefore, all attempts to search for editing interfering compounds have been focused on molecules that bind to proteins of the editing machinery. However, in analogy to other RNA-driven biochemical pathways it should be possible to stall the reaction by targeting its substrate RNAs. Here we demonstrate inhibition of editing by specific aminoglycosides. The molecules bind into the major groove of the gRNA/pre-mRNA editing substrates thereby causing a stabilization of the RNA molecules through charge compensation and an increase in stacking. The data shed light on mechanistic details of the editing process and identify critical parameters for the development of new trypanocidal compounds.
This thesis covers the analysis of radix sort, radix select and the path length of digital trees under a stochastic input assumption known as the Markov model.
The main results are asymptotic expansions of mean and variance as well as a central limit theorem for the complexity of radix sort and the path length of tries, PATRICIA tries and digital search trees.
Concerning radix select, a variety of different models for ranks are discussed including a law of large numbers for the worst case behavior, a limit theorem for the grand averages model and the first order asymptotic of the average complexity in the quantile model.
Some of the results are achieved by moment transfer techniques, the limit laws are based on a novel use of the contraction method suited for systems of stochastic recurrences.