Nachlassverzeichnisse im Netz – Ein Projekt der Bayerischen Staatsbibliothek

Nachlässe rücken in der wissenschaftlichen Forschung immer mehr in den Fokus, wie etwa die stark gestiegenen Nutzerzahlen der Bayerischen Staatsbibliothek (BSB) über die letzten Jahre hinweg deutlich zeigen. Umso wichtiger ist insbesondere für Bibliotheken mit umfangreichen und fachlich breit gestreuten Nachlassbeständen eine möglichst genaue Erschließung im Internet, um der wissenschaftlichen Forschung einen schnellen Zugriff auf diese unikalen Materialien zu ermöglichen. Bei der digitalen Bereitstellung und vernetzten Erschließung verfolgt die BSB mit ihren rund 1.100 Nachlässen eine doppelte Strategie. Einerseits wird versucht, ausgewählte Nachlässe im Verbundsystem Kalliope zu katalogisieren. Andererseits werden die Erschließungsdaten zu den bereits erschlossenen und den erst grob geordneten Nachlässen, die in Form von hand- oder maschinenschriftlichen Listen sowie als Wordlisten vorliegen, digitalisiert und über den Bibliothekskatalog online zur Verfügung gestellt, um den Nutzern die Möglichkeit zu geben, sich so über die vorhandenen Bestände zu informieren. Wie dieses Projekt genau durchgeführt wurde, ist Gegenstand des Artikels.Special collections and personal papers are becoming more and more important for academic research, as is shown clearly by the increasing usage numbers at the Bavarian State Library (BSB) over the last couple of years. Especially for libraries with extensive and manifold collections of estates, it is important to present these unique materials in a well-indexed manner on the internet, in order to give the scientific community easy access. The Bavarian State Library, which keeps more than 1.100 estates of personal papers, pursues a double strategy: On the one hand, selected estates are fully cataloged in the database “Kalliope”. As this procedure is likely to take a long time, the library on the other hand has been digitizing older hand- or typewritten lists with information about the personal papers, and presents this data together with Word doc lists via the Online Catalogue. The paper explains how this project was planned and implemented

Massively parallel profiling and predictive modeling of the outcomes of CRISPR/Cas9-mediated double-strand break repair.

Non-homologous end-joining (NHEJ) plays an important role in double-strand break (DSB) repair of DNA. Recent studies have shown that the error patterns of NHEJ are strongly biased by sequence context, but these studies were based on relatively few templates. To investigate this more thoroughly, we systematically profiled ∼1.16 million independent mutational events resulting from CRISPR/Cas9-mediated cleavage and NHEJ-mediated DSB repair of 6872 synthetic target sequences, introduced into a human cell line via lentiviral infection. We find that: (i) insertions are dominated by 1 bp events templated by sequence immediately upstream of the cleavage site, (ii) deletions are predominantly associated with microhomology and (iii) targets exhibit variable but reproducible diversity with respect to the number and relative frequency of the mutational outcomes to which they give rise. From these data, we trained a model that uses local sequence context to predict the distribution of mutational outcomes. Exploiting the bias of NHEJ outcomes towards microhomology mediated events, we demonstrate the programming of deletion patterns by introducing microhomology to specific locations in the vicinity of the DSB site. We anticipate that our results will inform investigations of DSB repair mechanisms as well as the design of CRISPR/Cas9 experiments for diverse applications including genome-wide screens, gene therapy, lineage tracing and molecular recording

Realistic protein-protein association rates from a simple diffusional model neglecting long-range interactions, free energy barriers, and landscape ruggedness

We develop a simple but rigorous model of protein-protein association kinetics based on diffusional association on free energy landscapes obtained by sampling configurations within and surrounding the native complex binding funnels. Guided by results obtained on exactly solvable model problems, we transform the problem of diffusion in a potential into free diffusion in the presence of an absorbing zone spanning the entrance to the binding funnel. The free diffusion problem is solved using a recently derived analytic expression for the rate of association of asymmetrically oriented molecules. Despite the required high steric specificity and the absence of long-range attractive interactions, the computed rates are typically on the order of 10^4-10^6 M-1 s-1, several orders of magnitude higher than rates obtained using a purely probabilistic model in which the association rate for free diffusion of uniformly reactive molecules is multiplied by the probability of a correct alignment of the two partners in a random collision. As the association rates of many protein-protein complexes are also in the 10^5-10^6 M-1 s-1, our results suggest that free energy barriers arising from desolvation and/or side-chain freezing during complex formation or increased ruggedness within the binding funnel, which are completely neglected in our simple diffusional model, do not contribute significantly to the dynamics of protein-protein association. The transparent physical interpretation of our approach that computes association rates directly from the size and geometry of protein-protein binding funnels makes it a useful complement to Brownian dynamics simulations.Comment: 9 pages, 5 figures, 1 table. One figure and a few comments added for clarificatio

Taxing away M&A : the effect of corporate capital gains taxes on acquisition activity

Taxing capital gains is an important obstacle to the efficient allocation of resources because it imposes a transaction cost on the vendor which locks in appreciated assets by raising the vendor’s reservation price in prospective transactions. For M&As, this effect has been intensively studied with regard to shareholder taxation, whereas empirical evidence on the effect of capital gains taxes paid by corporations is scarce. This paper analyzes how corporate level taxation of capital gains affects inter-corporate M&As. Studying several substantial tax reforms in a panel of 30 countries for the period of 2002-2013, we identify a significant lock-in effect. Results from estimating a Poisson pseudo-maximumlikelihood (PPML) model suggest that a one percentage point decrease in the corporate capital gains tax rate would raise both the number and the total deal value of acquisitions by about 1.1% per year. We use this result to estimate an efficiency loss resulting from corporate capital gains taxation of 3.06 bn USD per year in the United States

Tasks and localization of subject-specific pedagogy in scientific literature. A systematic approach to term use

Der Beitrag skizziert die Entwicklung einer Systematik der Auffassungen von «Fachdidaktik» in der wissenschaftlichen Literatur. Im Ergebnis werden die Aufgaben der Fachdidaktik am häufigsten in der Forschung gesehen. Sie wird zu ähnlichen Teilen zwischen bildungswissenschaftlichen und fachwissenschaftlichen Bezugsdisziplinen verortet. Ausgehend von Perspektiven der Wissenschaftsforschung, der Professionsforschung und der Allgemeinen Fachdidaktik werden die der Fachdidaktik zugeschriebenen Aufgaben und Verortungen diskutiert. Implikationen für mögliche Voraussetzungen der potenziellen Kooperation zwischen Fachdidaktiken (und Bildungswissenschaften) werden aufgezeigt. (DIPF/Orig.)The article outlines the development of a systematics of the conceptions of subjectspecific pedagogy in scientific literature. As the analysis shows, the tasks of subject-specific pedagogy are most often seen in research. Subject-specific pedagogy is localized to similar parts between educational science and their corresponding subject-related disciplines. The tasks and localizations attributed to subject-specific pedagogy are discussed based on the perspectives of the theory of science, profession-related research, and general subject-specific pedagogy. Implications for possible preconditions of potential forms of cooperation between different branches of subject-specific pedagogy (and educational sciences) are pointed out

Aufgaben und Verortungen der Fachdidaktik in wissenschaftlicher Literatur. Systematische Annäherung an den Begriffsgebrauch

Der Beitrag skizziert die Entwicklung einer Systematik der Auffassungen von «Fachdidaktik» in der wissenschaftlichen Literatur. Im Ergebnis werden die Aufgaben der Fachdidaktik am häufigsten in der Forschung gesehen. Sie wird zu ähnlichen Teilen zwischen bildungswissenschaftlichen und fachwissenschaftlichen Bezugsdisziplinen verortet. Ausgehend von Perspektiven der Wissenschaftsforschung, der Professionsforschung und der Allgemeinen Fachdidaktik werden die der Fachdidaktik zugeschriebenen Aufgaben und Verortungen diskutiert. Implikationen für mögliche Voraussetzungen der potenziellen Kooperation zwischen Fachdidaktiken (und Bildungswissenschaften) werden aufgezeigt

Protein interactions studied by SAXS: effect of ionic strength and protein concentration for BSA in aqueous solutions.

We have studied a series of samples of bovine serum albumin (BSA) solutions with protein concentration, c, ranging from 2 to 500 mg/mL and ionic strength, I, from 0 to 2 M by small-angle X-ray scattering (SAXS). The scattering intensity distribution was compared to simulations using an oblate ellipsoid form factor with radii of 17 × 42 × 42 Å, combined with either a screened Coulomb, repulsive structure factor, S SC (q), or an attractive square-well structure factor, S SW (q). At pH ) 7, BSA is negatively charged. At low ionic strength, I < 0.3 M, the total interaction exhibits a decrease of the repulsive interaction when compared to the salt-free solution, as the net surface charge is screened, and the data can be fitted by assuming an ellipsoid form factor and screened Coulomb interaction. At moderate ionic strength (0.3-0.5 M), the interaction is rather weak, and a hard-sphere structure factor has been used to simulate the data with a higher volume fraction. Upon further increase of the ionic strength (I g 1.0 M), the overall interaction potential was dominated by an additional attractive potential, and the data could be successfully fitted by an ellipsoid form factor and a square-well potential model. The fit parameters, well depth and well width, indicate that the attractive potential caused by a high salt concentration is weak and long-ranged. Although the long-range, attractive potential dominated the protein interaction, no gelation or precipitation was observed in any of the samples. This is explained by the increase of a short-range, repulsive interaction between protein molecules by forming a hydration layer with increasing salt concentration. The competition between long-range, attractive and shortrange, repulsive interactions accounted for the stability of concentrated BSA solution at high ionic strength

Pathophysiological role of prostanoids in coagulation of the portal venous system in liver cirrhosis

BACKGROUND: Prostanoids are important regulators of platelet aggregation and thrombotic arterial diseases. Their involvement in the development of portal vein thrombosis, frequent in decompensated liver cirrhosis, is still not investigated. METHODS: Therefore, we used pro-thrombotic venous milieu generation by bare metal stent transjugular intrahepatic portosystemic shunt insertion, to study the role of prostanoids in decompensated liver cirrhosis. Here, 89 patients receiving transjugular intrahepatic portosystemic shunt insertion were included in the study, and baseline levels of thromboxane B2, prostaglandin D2 and prostaglandin E2 were measured in the portal and the hepatic vein. RESULTS: While the hepatic vein contained higher levels of thromboxane B2 than the portal vein, levels of prostaglandin E2 and D2 were higher in the portal vein (all P<0.0001). Baseline concentrations of thromboxane B2 in the portal vein were independently associated with an increase of portal hepatic venous pressure gradient during short term follow-up, as an indirect sign of thrombogenic potential (multivariable P = 0.004). Moreover, severity of liver disease was inversely correlated with portal as well as hepatic vein levels of prostaglandin D2 and E2 (all P<0.0001). CONCLUSIONS: Elevated portal venous thromboxane B2 concentrations are possibly associated with the extent of thrombogenic potential in patients with decompensated liver cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03584204

The insect nephrocyte is a podocyte-like cell with a filtration slit diaphragm.

The nephron is the basic structural and functional unit of the vertebrate kidney. It is composed of a glomerulus, the site of ultrafiltration, and a renal tubule, along which the filtrate is modified. Although widely regarded as a vertebrate adaptation, 'nephron-like' features can be found in the excretory systems of many invertebrates, raising the possibility that components of the vertebrate excretory system were inherited from their invertebrate ancestors. Here we show that the insect nephrocyte has remarkable anatomical, molecular and functional similarity to the glomerular podocyte, a cell in the vertebrate kidney that forms the main size-selective barrier as blood is ultrafiltered to make urine. In particular, both cell types possess a specialized filtration diaphragm, known as the slit diaphragm in podocytes or the nephrocyte diaphragm in nephrocytes. We find that fly (Drosophila melanogaster) orthologues of the major constituents of the slit diaphragm, including nephrin, NEPH1 (also known as KIRREL), CD2AP, ZO-1 (TJP1) and podocin, are expressed in the nephrocyte and form a complex of interacting proteins that closely mirrors the vertebrate slit diaphragm complex. Furthermore, we find that the nephrocyte diaphragm is completely lost in flies lacking the orthologues of nephrin or NEPH1-a phenotype resembling loss of the slit diaphragm in the absence of either nephrin (as in human congenital nephrotic syndrome of the Finnish type, NPHS1) or NEPH1. These changes markedly impair filtration function in the nephrocyte. The similarities we describe between invertebrate nephrocytes and vertebrate podocytes provide evidence suggesting that the two cell types are evolutionarily related, and establish the nephrocyte as a simple model in which to study podocyte biology and podocyte-associated diseases.This work was supported by Wellcome Trust grants awarded to H.S. (072441 and 079221, H.W., B.D., H.S.); Deutsche Forschungsgemeinschaft (SFB 590) awarded to Elisabeth Knust (F.G.), ARC 1242 (H.W., B.D., H.S., F.G.); MEC grant awarded to M.R-G. (BFU2007-62201, S.P-S., M.R-G.); Fundación Ramón Areces grant to the CBMSO (M.R-G.); EC grant LSHG-CT-2004-511978 to MYORES (M.R-G.); an FPU fellowship from the MEC awarded to A.G-L.Peer reviewe