7,005 research outputs found

    Credit constraints and the propagation of the Great Depression in Germany

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    We evaluate the role played by loan supply shocks in the decline of investment and industrial production during the Great Depression in Germany from 1927 to 1932. We identify loan supply shocks in the context of a time varying parameter vector autoregression with stochastic volatility. Our results indicate that credit constraints were a significant driver of industrial production between 1927 and 1932, supporting the view that a structurally weak banking sector was an important contributor to the German Great Depression. We find further that loan supply shocks were an important driver of investment in the early phase of the depression, between 1927 and 1929, but not between 1930 and 1932. We suggest possible explanations for this puzzle and directions for future research

    The Effect of Melatonin or Maternal Nutrient Restriction on Cell Proliferation in the Ovine Placenta

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    Our objectives were to assess melatonin receptor dependent modulation of placental cell proliferation following treatment with either melatonin, luzindole (melatonin receptor 1 and 2 antagonist), or vehicle. In addition, a second study was conducted to assess placental cell proliferation following dietary melatonin treatment in a maternal nutrient restriction model. For the first experiment, 14 primiparous ewes were fitted with Alzet mini osmotic pumps attached to a catheter and infused with vehicle, melatonin, or luzindole from d 62 to 90 of gestation. Ewes were euthanized and placentomes collected for analysis at the end of the 4 week infusion. For the second experiment, 31 primiparous ewes were supplemented with 5 mg of melatonin per d (MEL) or no melatonin (CON) and allocated to receive 100% (adequate) or 60% (restricted) of their nutrient requirements from d 50 to 130 of gestation. On d 130 of gestation, ewes were euthanized and placentomes were collected for analysis. Placentomes from both experiment 1 and 2 were examined for percentage of proliferating cells using an immunofluorescence assay. A Ki-67 mouse monoclonal antibody was used to stain proliferating cells within each tissue section and was compared to non-proliferating cells stained with DAPI to determine the percentage of proliferating cells within each sample. Total RNA, DNA and protein was also analyzed within each sample. For experiment 1, cell proliferation in the cotyledon and caruncle was not affected (P \u3e 0.30) by vehicle, melatonin or luzindole infusions. Dietary melatonin supplementation from mid to late gestation may impact cotyledon cell proliferation; however chronic infusion of melatonin or luzindole did not change proliferation in either the cotyledon or caruncle. Treatment did not alter the concentrations of RNA, DNA, protein (P . 0.15), or the ratio of RNA:DNA and the ratio of protein:DNA (P . 0.17). For experiment 2, there was no melatonin supplementation by nutritional plane interactions (P \u3e 0.50) on cellular proliferation in either the cotyledon or caruncle. There was a tendency (P = 0.08) for melatonin supplemented ewes to have an increased percentage of proliferating cells in the cotyledon; however, this effect of melatonin was absent (P \u3e 0.30) in the caruncle. Nutritional plane did not alter cellular proliferation in either the cotyledon (P \u3e 0.70) or caruncle (P \u3e 0.50). There was no effect of nutritional plane or melatonin treatment on the concentration of DNA or protein (P . 0.21) in caruncular tissue. However there was an interaction on RNA (P = 0.02) in caruncular tissue which may be due to an increase in gene expression following melatonin treatment. There was no effect of treatment or nutritional plane on DNA, RNA, protein (P . 0.20) as well as no effect on RNA:DNA or protein:DNA (P . 0.25). In summary, melatonin may alter placental growth in ewes with IUGR; however, this needs further investigation

    Mapping Functionally Important and Stabilising Regions in Biotherapeutic Proteins, using NMR and Mutagenesis

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    Structure-function relationships in proteins refer to a trade-off between stability and bioactivity, moulded by evolution of the molecule. Identifying which protein amino acid residues jeopardise global or local stability for the benefit of bioactivity would reveal residues pivotal to this structure-function trade-off. Demonstrated here is the use of varied-temperature 15N-1H heteronuclear single quantum coherence (HSQC) nuclear magnetic resonance (NMR) spectroscopy to probe the microenvironment and dynamics of residues in granulocyte-colony stimulating factor (G-CSF). This experimental approach was also used to investigate (de-) stabilising mechanisms of action for previously studied excipients with G-CSF. Combining NMR with in silico analysis revealed four structural clusters that are subject to localised conformational changes (some of which are key to bioactivity) or partial unfolding prior to global unfolding at higher temperatures. Mechanisms by which excipients influence these important structural changes and implement their own structural clusters reflects their impact on stability and function. This approach was leveraged for semi-rational mutant/formulation design. These mutants were tested for fitness with respect to thermostability and functionality. The Mutants P65V and E45Q were constructed to elicit mutation-excipient interactions, and presented the largest impact on the respective fitness. Hence, this study proposes an approach to profile residues, thus highlighting their roles in stability and bioactivity while exposing potential mutation-excipient interactions. This permits a semi-rational protein engineering approach to optimise desirable protein fitness characteristics

    The interaction of knowledge sources in word sense disambiguation

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    Word sense disambiguation (WSD) is a computational linguistics task likely to benefit from the tradition of combining different knowledge sources in artificial in telligence research. An important step in the exploration of this hypothesis is to determine which linguistic knowledge sources are most useful and whether their combination leads to improved results. We present a sense tagger which uses several knowledge sources. Tested accuracy exceeds 94% on our evaluation corpus.Our system attempts to disambiguate all content words in running text rather than limiting itself to treating a restricted vocabulary of words. It is argued that this approach is more likely to assist the creation of practical systems

    Property Rights and Freedom: The Keys to Improving Life in Indian Country

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    American Indians are at the bottom of nearly every indicator of welfare and have been since the founding of the United States. The present paper focuses on but two of the causal agents: lack of private property rights and a dearth of economic freedom. Although addressing these issues will not solve all of Indian country’s problems, strengthening property rights and improving economic freedom will generate opportunities for American Indians to improve their economic and social well-being. This recommendation is easy to implement and aligns well with tribal culture pre-contact

    Spatially extended and high-velocity dispersion molecular component in spiral galaxies: single-dish vs. interferometric observations

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    Recent studies of the molecular medium in nearby galaxies have provided mounting evidence that the molecular gas can exist in two phases: one that is clumpy and organized as molecular clouds and another one that is more diffuse. This last component has a higher velocity dispersion than the clumpy one. In order to investigate these two molecular components further, we compare the fluxes and line widths of CO in NGC 4736 and NGC 5055, two nearby spiral galaxies for which high-quality interferometric as well as single-dish data sets are available. Our analysis leads to two main results: 1) Employing three different methods, we determine the flux recovery of the interferometer as compared to the single-dish to be within a range of 35-74% for NGC4736 and 81-92% for NGC5055, and 2) when focusing on high (SNR>5) lines of sight, the single-dish line widths are larger by ~(40+-20)% than the ones derived from interferometric data; which is in agreement with stacking all lines of sight. These results point to a molecular gas component that is distributed over spatial scales larger than 30"(~1kpc), and is therefore filtered out by the interferometer. The available observations do not allow us to distinguish between a truly diffuse gas morphology and a uniform distribution of small clouds that are separated by less than the synthesized beam size (~3" or ~100pc), as they would both be invisible for the interferometer. This high velocity dispersion component has a dispersion similar to what is found in the atomic medium, as traced through observations of the HI line.Comment: 12 pages, 5 figures, Accepted to A
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