Comparisons among the five ground-motion models developed using RESORCE for the prediction of response spectral accelerations due to earthquakes in Europe and the Middle East

This article presents comparisons among the five ground-motion models described in other articles within this special issue, in terms of data selection criteria, characteristics of the models and predicted peak ground and response spectral accelerations. Comparisons are also made with predictions from the Next Generation Attenuation (NGA) models to which the models presented here have similarities (e.g. a common master database has been used) but also differences (e.g. some models in this issue are nonparametric). As a result of the differing data selection criteria and derivation techniques the predicted median ground motions show considerable differences (up to a factor of two for certain scenarios), particularly for magnitudes and distances close to or beyond the range of the available observations. The predicted influence of style-of-faulting shows much variation among models whereas site amplification factors are more similar, with peak amplification at around 1s. These differences are greater than those among predictions from the NGA models. The models for aleatory variability (sigma), however, are similar and suggest that ground-motion variability from this region is slightly higher than that predicted by the NGA models, based primarily on data from California and Taiwan

Comparisons among the five ground-motion models developed using RESORCE for the prediction of response spectral accelerations due to earthquakes in Europe and the Middle East

This article presents comparisons among the five ground-motion models described in other articles within this special issue, in terms of data selection criteria, characteristics of the models and predicted peak ground and response spectral accelerations. Comparisons are also made with predictions from the Next Generation Attenuation (NGA) models to which the models presented here have similarities (e.g. a common master database has been used) but also differences (e.g. some models in this issue are nonparametric). As a result of the differing data selection criteria and derivation techniques the predicted median ground motions show considerable differences (up to a factor of two for certain scenarios), particularly for magnitudes and distances close to or beyond the range of the available observations. The predicted influence of style-of-faulting shows much variation among models whereas site amplification factors are more similar, with peak amplification at around 1s. These differences are greater than those among predictions from the NGA models. The models for aleatory variability (sigma), however, are similar and suggest that ground-motion variability from this region is slightly higher than that predicted by the NGA models, based primarily on data from California and Taiwan

Distinct roles for Arabidopsis SUMO protease ESD4 and its closest homolog ELS1

SUMO conjugation affects a broad range of processes in Arabidopsis thaliana, including flower initiation, pathogen defense, and responses to cold, drought and salt stress. We investigated two sequence-related SUMO-specific proteases that are both widely expressed and show that they differ significantly in their properties. The closest homolog of SUMO protease ESD4, ESD4-LIKE SUMO PROTEASE 1 (ELS1, alternatively called AtULP1a) has SUMO-specific proteolytic activity, but is functionally distinct from ESD4, as shown by intracellular localization, mutant phenotype and heterologous expression in yeast mutants. Furthermore, we show that the growth defects caused by loss of ESD4 function are not due to increased synthesis of the stress signal salicylic acid, as was previously shown for a SUMO ligase, indicating that impairment of the SUMO system affects plant growth in different ways. Our results demonstrate that two A. thaliana SUMO proteases showing close sequence similarity have distinct in vivo functions

Beeinflusst der Vorwissensstand die Interaktionsdynamik und den Lernerfolg im digitalen problemorientierten Lernen? Eine Pilotstudie

Objective: Previous research on problem-based learning (PBL) describes that videotaped observations develop meaningful insights into cognitive processes in tutorial groups. Analysis regarding the amount of prior knowledge on learning achievement has not been investigated in medical education so far, although both are key factors of PBL success. Thus, we intended to analyse videos of digital problem-based learning (dPBL) sessions, focusing on knowledge acquisition and interaction dynamics among groups with different levels of prior knowledge to reveal any distinctions.Methods: This study employed a pilot design by dividing 60 dental students into twelve subgroups with less or more prior knowledge, determined by a pre-semester multiple choice test (MCQ). The groups engaged in videotaped dPBL cases, which were examined regarding group interactions and tutor effectiveness. The learning achievement was assessed through a post-semester MCQ, an oral and practical exam.Results: The video analysis showed that dPBL groups with less prior knowledge achieved significantly higher tutor effectiveness and group interaction utterances, but that the percentage of time in which utterances occurred was similar in both groups. Related to the MCQ results, the students with less prior knowledge learned four times more than those with profound previous abilities, but no significant difference was found in the results of the oral exam and practical exam.Conclusions: The interaction dynamics in dPBL depend on the group's amount of prior knowledge. Especially groups including participants with less prior knowledge seemed to benefit from dPBL in comparison to groups with more prior knowledge. The dPBL groups acquired knowledge in different ways during the courses but, finally, all students arrived at a similar level of knowledge.Zielsetzung: Forschungsbefunde zum problemorientierten Lernen (POL) zeigen, dass Untersuchungen von Videoaufzeichnungen tutorieller Lernsitzungen bedeutsame Einblicke in kognitive Prozesse ermöglichen. Der Einfluss von Vorwissen auf Lernerfolg unter Einbezug der Lehr-Lern-Interaktionsdynamik wurde in der medizinischen Ausbildung bisher allerdings noch nicht untersucht, obwohl die Faktoren eine Schlüsselrolle für den Erfolg von POL darstellen. Ziel der Studie ist es daher, digitale problemorientierten Lernsitzungen (dPOL) anhand von Videoaufzeichnungen zu analysieren und dabei Wissenserwerbsprozesse und die Interaktionsdynamik in den Lerngruppen in Abhängigkeit vom Vorwissensstand zu untersuchen.Methoden: In dieser Studie wurde ein Pilotdesign angewandt, bei dem 60 Zahnmedizinstudierende in zwölf Untergruppen mit geringerem oder höherem Vorwissen eingeteilt wurden. Die Erhebung des Vorwissens erfolgte durch einen Multiple-Choice-Test (MCQ) zu Beginn des Semesters. Die Gruppen bearbeiteten mit tutorieller Unterstützung dPOL-Fälle. Die Gruppeninteraktion und Tutor*innenaktivitäten wurden videographiert. Der Lernerfolg wurde am Ende des Semesters anhand eines MCQ sowie einer mündlichen und praktischen Prüfung erhoben.Ergebnisse: dPOL-Gruppen mit geringerem Vorwissen weisen eine signifikant höhere Anzahl an Aussagen in Gruppeninteraktionen und eine höhere Tutor*inneneffektivität auf. Der zeitliche Umfang der Äußerungen (Prozentsatz, die Äußerungen an der Gesamtzeit einnehmen) ist jedoch in beiden Gruppen gleich. Studierende mit geringerem Vorwissen zeigen einen höheren Lernzuwachs im MCQ. Signifikante Gruppenunterschiede in den Ergebnissen der mündlichen und praktischen Prüfung zeigen sich allerdings nicht.Schlussfolgerungen: Unterschiedliches Vorwissen der Lernenden führt zu unterschiedlichen Interaktionsdynamiken im dPOL. Im Hinblick auf Lernoutcomes profitieren insbesondere Lernende mit geringerem Vorwissen von dPOL. Die jeweiligen dPOL-Gruppen erreichten am Ende des Semesters ähnliche Lernergebnisse, die Befunde legen aber nahe, dass sich die Charakteristik des Wissenserwerbprozesses in Abhängigkeit vom Vorwissen unterscheidet

Enhanced biodegradation at the Landgraaf bioreactor test-cell

From 2001 to 2011, a bioreactor demonstration was performed in a 25,000 m3 (8 m deep, 3500 m2 surface) test-cell. In this bioreactor, biodegradation was enhanced by premixing and homogenizing of waste, recirculation of leachate and aeration. Anaerobic biodegradation was completed within four years and was followed by two years of aeration. Ultimately a residue was obtained that had lost approximately 95% of its biogas potential. Biodegradation resulted in a significantly reduced leaching potential for dissolved organic carbon (DOC) and specific heavy metals. For other inorganic components, less progress was achieved. Increased flushing would be required for further reduction of the leaching potential. A significant reduction in chemical oxygen demand (COD) and ammonia (NH+4) in leachate was not demonstrated during the relative short-term aeration: COD concentrations actually increased slightly and there was no effect on NH+4. During the project, it became clear that moisture flow through the waste followed preferential flow paths. Therefore, attention was also paid to gain better understanding of leachate flows. From a tracer test, it was concluded that part of the waste contaminants are held in immobile blocks and are to a large extent unaffected by flow occurring in the surrounding preferential flow paths

Human tetherin exerts strong selection pressure on the HIV-1 group N Vpu protein

HIV-1 groups M and N emerged within the last century following two independent cross-species transmissions of SIVcpz from chimpanzees to humans. In contrast to pandemic group M strains, HIV-1 group N viruses are exceedingly rare, with only about a dozen infections identified, all but one in individuals from Cameroon. Poor adaptation to the human host may be responsible for this limited spread of HIV-1 group N in the human population. Here, we analyzed the function of Vpu proteins from seven group N strains from Cameroon, the place where this zoonosis originally emerged. We found that these N-Vpus acquired four amino acid substitutions (E15A, V19A and IV25/26LL) in their transmembrane domain (TMD) that allow efficient interaction with human tetherin. However, despite these adaptive changes, most N-Vpus still antagonize human tetherin only poorly and fail to down-modulate CD4, the natural killer (NK) cell ligand NTB-A as well as the lipid-antigen presenting protein CD1d. These functional deficiencies were mapped to amino acid changes in the cytoplasmic domain that disrupt putative adaptor protein binding sites and an otherwise highly conserved beta TrCP-binding DSGxxS motif. As a consequence, N-Vpus exhibited aberrant intracellular localization and/or failed to recruit the ubiquitin-ligase complex to induce tetherin degradation. The only exception was the Vpu of a group N strain recently discovered in France, but originally acquired in Togo, which contained intact cytoplasmic motifs and counteracted tetherin as effectively as the Vpus of pandemic HIV-1 M strains. These results indicate that HIV-1 group N Vpu is under strong host-specific selection pressure and that the acquisition of effective tetherin antagonism may lead to the emergence of viral variants with increased transmission fitness

The Vpu of an HIV-1 N strain from Togo is an effective tetherin antagonist.

<p>(<b>A</b>) Schematic representation of the origin of N1FR2011. This group N infection was diagnosed in Paris in a 57-year old male, 8 days after returning from Togo <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003093#ppat.1003093-Delaugerre1" target="_blank">[3]</a>. All other HIV-1 N infections were identified in individuals from Cameroon. (<b>B</b>) Evolutionary relationships among HIV-1 and SIVcpz Env amino acid sequences. Group N viruses are highlighted in blue; those containing an intact DSGxxS motif in their Vpu protein are labelled with an asterisk. The tree was inferred using maximum likelihood methods <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003093#ppat.1003093-Guindon1" target="_blank">[58]</a> using a JTT+I+G+F model <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003093#ppat.1003093-Jones1" target="_blank">[59]</a> chosen using ProtTest <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003093#ppat.1003093-Abascal1" target="_blank">[60]</a>. Numbers on branches indicate bootstrap support (only values above 70% are shown). The scale bar indicates 0.05 substitutions per site. (<b>C</b>) Comparison of the N1FR2011, 2693BA and YBF30 and N-Vpu protein sequences. As indicated, the N1FR2011 Vpu contains intact AxxxAxxxxxLL, DSGxxS and E/DxxxLL/I/V/M sites and a membrane proximal lysine residue (yellow). Dots specify amino acid identity and dashes gaps introduced to improve the alignment. (<b>D</b>) Efficient interaction of the N1FR2011 Vpu with ß-TrCP. 293T cells were transfected with plasmids expressing Vpu-N-Luc and C-Luc-ß-TrCP fusions and luciferase activity determined as described in the legend of <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003093#ppat-1003093-g004" target="_blank">Figure 4</a>. Shown is the comparison of the luciferase activity obtained for the N1FR2011 Vpu in comparison to group M (n = 3) and N (n = 7) Vpus. Each allele was measured in triplicate and shown are averages ±SDs. (<b>E</b>) Efficiency of downmodulation of tetherin in the presence of constructs expressing the indicated Vpus relative to those measured in cells transfected with the eGFP control vector. Values are averages (±SD) derived from three experiments. (<b>F to H</b>) Comparison of the effect of N1FR2011 and group N (n = 6) or M (n = 3) Vpu proteins on (<b>F</b>) infectious virus production or (<b>G, H</b>) viral p24 antigen release determined by (<b>G</b>) Western blot or (<b>H</b>) ELISA. Values represent the average infection levels or quantities of p24 antigen (n = 3) obtained in the presence of tetherin relative to those obtained in the absence of the restriction factor (100%). Percentages of cell-free p24 were normalized to the levels of cell-associated p24 antigen.</p

Functional characterization of Vpus from Cameroonian HIV-1 N strains.

<p>(<b>A</b>) FACS analysis of 293T cells cotransfected with tetherin, CD4, CD1d or NTB-A expression vectors and pCGCG plasmids expressing eGFP alone (lanes 2 and 3) or together with the indicated <i>vpu</i> allele (lanes 4 to 9). eGFP expression levels used to calculate receptor downmodulation and the mean fluorescence intensities (MFIs) are indicated. (<b>B</b>) Effect of various Vpus on infectious virus release. 293T cells were cotransfected with HIV-1 ΔVpu NL4-3 (2 µg), pCGCG vectors coexpressing eGFP and Vpu (500 ng), and a construct expressing HU tetherin (125 ng). Viral supernatants were obtained two days later and used to measure the quantity of infectious HIV-1 in the culture supernatants by infecting TZM-bl indicator cells. Shown is the infectious virion yield relative to that obtained in the absence of tetherin (100%). The results were confirmed in two independent experiments and each symbol indicates infectious virus yield in the presence of one of the 25 <i>vpu</i> alleles analyzed. (<b>C–F</b>) Vpu-dependent reduction of (<b>C</b>) tetherin, (<b>D</b>) CD4, (<b>E</b>) CD1d and (<b>F</b>) NTB-A surface expression in 293T cells. Shown is the reduction in the levels of receptor cell surface expression relative to those measured in cells transfected with the eGFP only control vector. Each symbol represents n-fold downmodulation of the indicated receptor molecule by one individual <i>vpu</i> allele examined. Shown are average values derived from three experiments. <i>Vpu</i> alleles derived from HIV-1 M are color coded red, N blue (except for the DJO0131 Vpu highlighted in green) and SIVcpz black; those shown in panel A are indicated by open symbols in panels B to F.</p

Most N-Vpus lack a functional ß-TrCP binding site.

<p>(<b>A</b>) Alignment of N-Vpu sequences. The NL4-3 Vpu amino acid sequence is shown on top for comparison. The AxxxAxxxW and AxxxAxxxxxLL residues that are important for anti-tetherin activity of M- and N-Vpus, respectively, a lysine residue that may be required for efficient tetherin antagonism <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003093#ppat.1003093-Yamaguchi2" target="_blank">[48]</a>, the DSGxxS ß-TrCP interaction site and an E/DxxxLL/I/V/M motif involved in targeting of tetherin for endosomal degradation <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003093#ppat.1003093-Mangeat1" target="_blank">[42]</a> are indicated in yellow. Dots specify amino acid identity and dashes represent gaps introduced to improve the alignment. (<b>B</b>) Interaction of Vpu with ß-TrCP. 293T cells were transfected with equal amounts of plasmids expressing ß-TrCP N-terminally fused to the C-terminal fragment of click beetle green and Vpu C-terminally fused to the N-terminal fragment of click beetle green. ß-catenin served as positive control. After 36 h, click beetle Luciferase activity was determined in living cells by addition of D-Luciferin and quantification of bioluminescence. (<b>C</b>) Interaction of Vpu with CD4. 293T cells were transfected with plasmids expressing CD4 C-terminally fused to the C-terminal fragment of click beetle green and Vpu C-terminally fused to the N-terminal fragment of click beetle green and interaction efficiencies were determined as described in panel C. To exclude a bias baused by Vpu-mediated degradation of CD4, a dominant negative mutant of β-TrCP1 isoform 2 lacking the F-box (amino acids 141–193) was cotransfected in a control experiment. This mutant still binds Vpu but lacks the Fbox domain and thus fails to recruit the E3 ubiquitin ligase complex. (<b>D</b>) Effect of mutations in the DSGxxS motif of HIV-1 M and N Vpus on infectious virus release in the presence of tetherin. Curves represent the average infection values (n = 3) relative to those obtained in the absence of tetherin (100%). (<b>E</b>) Mutations in the ß-TrCP binding site of the M- but not N-Vpu impair tetherin degradation. 293T cells were cotransfected with plasmids expressing the indicated <i>vpu</i> alleles and tetherin. Steady state expression levels of tetherin were determined two days later by Western blot analysis. The numbers provided below give the intensities of the tetherin signals relative to the eGFP control lane and were normalized for the ß-actin signal intensity. The results were confirmed in an independent experiment. (<b>F to I</b>) Effect of changes in the ß-TrCP binding site of Vpu on down-modulation of tetherin and various receptors. Shown is the Vpu-dependent reduction of (<b>F</b>) tetherin, (<b>G</b>) CD4, (<b>H</b>) CD1d and (<b>I</b>) NTB-A surface expression in 293T cells relative to those measured in cells transfected with the eGFP only control vector. Values represent averages (±SD) derived from two independent experiments.</p