Würzburg als Stadt am Main vom Hochmittelalter bis ins frühe 19. Jahrhundert

In den vier Hauptkapiteln dieses Beitrags sollen die wichtigsten Aspekte der Rolle Würzburgs als Stadt am Main dargestellt werden. „Furt und Brücke“ steht für den hier den Fluss kreuzenden Landverkehr als einer entscheidenden Ursache für die Stadtentstehung an dieser Stelle und die weitere Stadtentwicklung. Unter „Wehr und Schleuse“ werden Schifffahrt und Flößerei sowie wasserbauliche Maßnahmen behandelt, die sowohl für die Schifffahrt als auch für Mühlen und Hammerwerke von Bedeutung waren. Bei „Mühle und Reuse“ geht es um die technische Nutzung der Wasserkraft, insbesondere in der Frühen Neuzeit, und die Bedeutung und Traditionen der städtischen Fischerei. „Zoll und Stapel“ stehen für die Organisation der steuerlichen Abschöpfung der Erträge des Warenverkehrs auf dem Main und den ihn kreuzenden Straßen durch die Fürstbischöfe und die Stadt und den Gewinn, den sie daraus zogen.Würzburg, a City on the Main River from the High Middle Ages to the Early 19th CenturyThis paper tries to cover the main aspects of Würzburg’s role as a riverine city in four main chapters. “Furt und Brücke” (ford and bridge) stand for the land traffic crossing the river here which was one of the main reasons for the emergence of the city at this spot and the city’s further development. “Wehr und Schleuse” (weir and lock) stand for the river traffic, i.e. rafting and shipping as well as for activities in hydraulic engineering which aimed at an improved efficiency of flour mills and hammermills. „Mühle und Reuse“ (mill and fish trap) deal with the mills on the river and with a typically mercantilist „industrial centre“ built at the upper end of the weir in the 17th century, as well as with the importance and the traditions of the local fishery. „Zoll und Stapel“ (toll and staple) describe typical forms of trade and its taxation in the Middle Ages and the early Modern Age.Würzburg jako miasto nad Menem w okresie od pełnego średniowiecza do początków XIX wiekuW czterech głównych częściach tego artykułu omówiono najważniejsze aspekty roli Würzburga jako miasta nad rzeką. „Furt und Brücke” (bród i most) dotyczy krzyżującego się tu ruchu lądowego jako jednego z decydujących przyczyn powstania miasta i jego dalszego rozwoju. W „Wehr und Schleuse” (tama i śluza) przedstawiono żeglugę statków i flisactwo oraz przedsięwzięcia budowlane, które miały znaczenie zarówno dla żeglugi, jak i młynów. Przy „Mühle und Reuse” (młyn i więcierz) chodzi o techniczne wykorzystywanie siły wody, szczególnie w nowożytności, oraz znaczenie i tradycje rybołówstwa miejskiego. „Zoll und Stapel” (cło i skład) dotyczy organizacji pobierania podatków od dochodów z ruchu towarów na Menie i krzyżujących się z nim drogach przez księcia biskupa oraz miasto, a także zysków, które z tego wynikały. Tłumaczenie Renata Skowrońsk

A calibrated diversity assay for nucleic acid libraries using DiStRO—a Diversity Standard of Random Oligonucleotides

We have determined diversities exceeding 1012 different sequences in an annealing and melting assay using synthetic randomized oligonucleotides as a standard. For such high diversities, the annealing kinetics differ from those observed for low diversities, favouring the remelting curve after annealing as the best indicator of complexity. Direct comparisons of nucleic acid pools obtained from an aptamer selection demonstrate that even highly complex populations can be evaluated by using DiStRO, without the need of complicated calculations

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen

Plasmodium vivax Invasion of Human Erythrocytes Inhibited by Antibodies Directed against the Duffy Binding Protein

Christopher King and colleagues found that both rabbit and human antibodies inhibited binding of rPvDBPII to the Duffy antigen N-terminal region and to Duffy-positive human erythrocytes, suggesting that a PvDBP-based vaccine may reduce blood stage Plasmodium vivax infection

All-sky search for time-integrated neutrino emission from astrophysical sources with 7 years of IceCube data

Since the recent detection of an astrophysical flux of high energy neutrinos, the question of its origin has not yet fully been answered. Much of what is known about this flux comes from a small event sample of high neutrino purity, good energy resolution, but large angular uncertainties. In searches for point-like sources, on the other hand, the best performance is given by using large statistics and good angular reconstructions. Track-like muon events produced in neutrino interactions satisfy these requirements. We present here the results of searches for point-like sources with neutrinos using data acquired by the IceCube detector over seven years from 2008--2015. The discovery potential of the analysis in the northern sky is now significantly below $E_\nu^2d\phi/dE_\nu=10^{-12}\:\mathrm{TeV\,cm^{-2}\,s^{-1}}$, on average $38\%$ lower than the sensitivity of the previously published analysis of four years exposure. No significant clustering of neutrinos above background expectation was observed, and implications for prominent neutrino source candidates are discussed.Comment: 19 pages, 17 figures, 3 tables; ; submitted to The Astrophysical Journa

The contribution of Fermi-2LAC blazars to the diffuse TeV-PeV neutrino flux

The recent discovery of a diffuse cosmic neutrino flux extending up to PeV energies raises the question of which astrophysical sources generate this signal. One class of extragalactic sources which may produce such high-energy neutrinos are blazars. We present a likelihood analysis searching for cumulative neutrino emission from blazars in the 2nd Fermi-LAT AGN catalogue (2LAC) using an IceCube neutrino dataset 2009-12 which was optimised for the detection of individual sources. In contrast to previous searches with IceCube, the populations investigated contain up to hundreds of sources, the largest one being the entire blazar sample in the 2LAC catalogue. No significant excess is observed and upper limits for the cumulative flux from these populations are obtained. These constrain the maximum contribution of the 2LAC blazars to the observed astrophysical neutrino flux to be $27 \%$ or less between around 10 TeV and 2 PeV, assuming equipartition of flavours at Earth and a single power-law spectrum with a spectral index of $-2.5$. We can still exclude that the 2LAC blazars (and sub-populations) emit more than $50 \%$ of the observed neutrinos up to a spectral index as hard as $-2.2$ in the same energy range. Our result takes into account that the neutrino source count distribution is unknown, and it does not assume strict proportionality of the neutrino flux to the measured 2LAC $\gamma$-ray signal for each source. Additionally, we constrain recent models for neutrino emission by blazars.Comment: 18 pages, 22 figure