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"A groundbreaking decision"
(2018)
PELDOR (pulse electron-electron double resonance) is an established method to study intramolecular distances and can give evidence for conformational changes and flexibilities. However, it can also be used to study intermolecular interactions as for example oligerimization. Here, we used PELDOR to study the ‘end-to-end’ stacking of small double stranded (ds)RNAs. For this study, the dsRNA molecules were only singly labelled with the spin label TPA to avoid multi-spin effects and to measure only the intermolecular stacking interactions. It can be shown that small dsRNAs tend to assemble to rod-like structures due to π-π-interactions between the base pairs at the end of the strands. On the one hand, these interactions can influence or complicate measurements aimed at the determining of the structure and dynamics of the dsRNA molecule itself. On the other hand, it can be interesting to study such intermolecular stacking interactions in more detail, as for example their dependence on ion concentration. We quantitatively determined the stacking probability as a function of the monovalent NaCl salt and the dsRNA concentration. From this data the dissociation constant Kd was deduced and found to depend on the ratio between the NaCl salt and dsRNA concentrations. Additionally, the distances and distance distributions obtained predict a model for the stacking geometry of dsRNAs. Introducing a nucleotide overhangs at one end of the dsRNA molecule restricts the stacking to the other end, leading only to dimer formations. Introducing such an overhang at both ends of the dsRNA molecule fully suppresses stacking, as we could demonstrate by PELDOR experiments quantitatively.
'Enough'-/'too'-constructions (E/T constructions) have an implicative reading: e.g., "Mary was clever enough to leave early yesterday" entails Mary left early yesterday. I argue that this implicative reading is not due to the lexical semantics proper of 'enough'/'too', but due to its bi-clausal structure (e.g., the above-mentioned example is analyzed as "Mary left early yesterday because she was clever enough"). I analyze 'enough' and 'too' simply as degree modifiers that involve a comparison: 'enough' means reaching the lower bound of an interval, while 'too' means exceeding the upper bound of an interval. Then inspired by Schulz (2011), Baglini and Francez (2015), and Nadathur (2016), I relate the semantics of E/T constructions to causal dependence: due to some sufficiency/excess, the infinitival complement clause in E/T constructions is episodically or generically (depending on its aspect being perfective or imperfective) true/false. I also argue that this infinitive has its tense and aspect marked on the main predicate of sentences, resulting in the seeming correlation between aspect and implication in languages that overtly make a distinction between perfective and imperfective aspects (e.g., French).
We assess the relationship between finance and growth over the period 1980-2014. We estimate a cross-country growth regression for 48 countries during 20 periods of 15 years starting in 1980 (to 1995) and ending in 1999 (to 2014). We use OLS and IV estimations and we find that: 1) overall financial development had a positive effect on economic growth during all periods of our sample, i.e., we confirm that from 1980 to 2014 financial services provided by the various financial systems were significant (to various degrees) for firm creation, industrial expansion and economic growth; but that, 2) the structure of financial markets was particularly relevant for economic growth until the financial crisis; while 3) the structure of the banking sector played a major role since; and finally that, 4) the legal system is the primary determinant of the effectiveness of the overall financial system in facilitating innovation and growth in (almost) all of our sample period. Hence, overall our results suggest that the relationship between finance and growth matters but also that it varies over time in strength and in sector origination.
JEL Classification: O16, G16, G20.
The paper proposes a new semantics for good-predications involving finite if -and that-clauses. The proposal combines a standard semantics for conditionals with a standard semantics for the positive form of gradable adjectives and a minimal semantics for modal good. The predicted truth-conditions and conditions of use solve the mood puzzle presented in the first part of the paper. The remainder of the paper defends the classical notion of comparative goodness in terms of a comparison between possible worlds against Lassiter (2017)’s challenge.
Based on an original dataset of 100 important pieces of legislation passed during the three presidencies of William J. Clinton, George W. Bush, and Barack H. Obama (1992-2013), this study explores two sets of questions:
(1) How do presidents influence legislators in Congress in the legislative arena, and what factors have an effect on the legislative strategies presidents choose?
(2) How successful are presidents in getting their policy positions enacted into law, and what configurations of institutional and actor-centered conditions determine presidential legislative success?
The analyses show that in an hyper-polarized environment, presidents usually have to fight an uphill-battle in the legislative arena, getting more involved if they face less favorable contexts and the odds are against them.
Moreover, the analyses suggest that there is no silver-bullet approach for presidents' legislative success. Instead, multiple patterns of success exist as presidents - depending on the institutional and public environment - can resort to different combinations of actions in order to see their preferred policy outcomes enacted.
My study examined MMA training, and thereby the ‘back region’ of MMA, where the ‘everyday life’ of MMA takes place. I enquired into how MMA training corresponds with MMA’s self-description, namely the somehow self-contradicting notion that MMA fights would be dangerous combative goings-on of approximately real fighting, but that MMA fighters would be able to approach these incalculable and uncontrolla-ble combative dangers as calculable and controllable risks.235 Conducting an ethnog-raphy in which I focused on the combination of participation and observation, I stud-ied how the specific interaction organisations of the three core training practices of MMA training provide the training students with specific combative experiences and how they thereby construct the social reality that is MMA training....
Depiction verbs such as paint license i(mage)- and p(ortrait)-readings; for instance, Ben painted a cow can convey that Ben produced an image of an unspecific cow or a portrait of a specific cow. This paper takes issue with a property-based intensional analysis of depiction verbs (Zimmermann, 2006b, 2016) and instead argues for an extensional account. Accordingly, the i-reading is rooted in the introduction of worldly representations by the explicit noun cow as such, whereas the p-reading is rooted in the interpolation of an implicit representation via coercion. This take on the ambiguity captures the following key traits. On i-readings, only representations are accessible to quantifiers and anaphors; moreover, intensional effects such as substitution failure disappear once ordinary objects and representations are adequately distinguished. P-readings, by contrast, involve representations that depend on the portrayed ordinary objects as particulars; correspondingly, only ordinary objects are accessible to quantifiers and anaphors. The proposal is spelled out in Asher’s (2011) Type Composition Logic.
Background: The rate of caesarean sections increased in the last decades to about 30% of births in western populations. Many caesarean sections are electively planned without an urgent medical reason for mother or child. Especially in women with a foregoing caesarean section, the procedure is planned early. An early caesarean section though may harm the newborn. Our aim is to evaluate the gestational time point after the 37th gestational week (after prematurity = term) of performing an elective caesarean section with the lowest morbidity for mother and child.
Methods: This is an update of a systematic review previously carried out on behalf of the German Federal Ministry of Health. We will perform a systematic literature search in MEDLINE, EMBASE, CENTRAL and CINAHL. Our primary outcome is the rate of admissions to the neonatal intensive care unit in early versus late term neonates. We will include (quasi) randomized controlled trials and cohort studies. The studies should include pregnant women who have an elective caesarean section at term. We will screen titles and abstracts and the identified full texts of studies for eligibility. Risk of bias will be assessed with the Cochrane Risk of Bias Tool for Randomized Trials or with the Risk of Bias Tool for Non-Randomized Studies of Interventions (ROBINS-I). These tasks will be performed independently by two reviewers. Data will be extracted in beforehand piloted extraction tables. A dose-response meta-analysis will be performed.
Discussion: Our aim is to reach a higher validity in the assessment of the time point of elective caesarean sections by performing a meta-analysis to support recommendations for clinical practice. We assume to identify less randomized controlled trials but a large number of cohort studies analyzing the given question. We will discuss similarities and differences in included studies as well as methodological strengths and weaknesses.
Systematic review registration: PROSPERO CRD42017078231
Objectives: The authors sought to evaluate the performance of the Ranger paclitaxel-coated balloon versus uncoated balloon angioplasty for femoropopliteal lesions at 12 months.
Background: Drug-coated balloons (DCBs) are a promising endovascular treatment option for peripheral artery disease of the femoropopliteal segment, and each unique device requires dedicated clinical study.
Methods: The prospective, randomized RANGER SFA (Comparison of the Ranger™ Paclitaxel-Coated PTA Balloon Catheter and Uncoated PTA Balloons in Femoropopliteal Arteries) study (NCT02013193) enrolled 105 patients with symptomatic lower limb ischemia (Rutherford category 2 to 4) and stenotic lesions in the nonstented femoropopliteal segment at 10 European centers. Seventy-one patients (mean age 68 ± 8 years, n = 53 men) were enrolled in the Ranger DCB arm, and 34 patients (mean age 67 ± 9 years, n = 23 men) were assigned to the control group. Twelve-month analysis included patency, safety, and clinical outcomes and quality-of-life assessments.
Results: The DCB group had a greater primary patency rate at 12 months (Kaplan-Meier estimate 86.4% vs. 56.5%), with a significantly longer time to patency failure (log-rank p < 0.001). The estimated freedom from target lesion revascularization rate was 91.2% in the DCB group and 69.9% in the control group at 12 months, with a significantly longer time to reintervention (p = 0.010). No target limb amputations or device-related deaths occurred in either group.
Conclusions: Twelve-month results show that patency was maintained longer after Ranger DCB treatment than after conventional balloon angioplasty, and this result was associated with a low revascularization rate and good clinical outcomes.
The long-chain fatty acid receptor FFAR1 is highly expressed in pancreatic β-cells. Synthetic FFAR1 agonists can be used as antidiabetic drugs to promote glucose-stimulated insulin secretion (GSIS). However, the physiological role of FFAR1 in β-cells remains poorly understood. Here we show that 20-HETE activates FFAR1 and promotes GSIS via FFAR1 with higher potency and efficacy than dietary fatty acids such as palmitic, linoleic, and α-linolenic acid. Murine and human β-cells produce 20-HETE, and the ω-hydroxylase-mediated formation and release of 20-HETE is strongly stimulated by glucose. Pharmacological inhibition of 20-HETE formation and blockade of FFAR1 in islets inhibits GSIS. In islets from type-2 diabetic humans and mice, glucose-stimulated 20-HETE formation and 20-HETE-dependent stimulation of GSIS are strongly reduced. We show that 20-HETE is an FFAR1 agonist, which functions as an autocrine positive feed-forward regulator of GSIS, and that a reduced glucose-induced 20-HETE formation contributes to inefficient GSIS in type-2 diabetes.
Rationale: Classic histology is the gold standard for vascular network imaging and analysis. The method however is laborious and prone to artefacts. Here, the suitability of ultramicroscopy (UM) and micro-computed tomography (CT) was studied to establish potential alternatives to histology.
Methods: The vasculature of murine organs (kidney, heart and atherosclerotic carotid arteries) was visualized using conventional 2D microscopy, 3D light sheet ultramicroscopy (UM) and micro-CT. Moreover, spheroid-based human endothelial cell vessel formation in mice was quantified. Fluorescently labeled Isolectin GS-IB4 A647 was used for in vivo labeling of vasculature for UM analysis, and analyses were performed ex vivo after sample preparation. For CT imaging, animals were perfused postmortem with radiopaque contrast agent.
Results: Using UM imaging, 3D vascular network information could be obtained in samples of animals receiving in vivo injection of the fluorescently labeled Isolectin GS-IB4. Resolution was sufficient to measure single endothelial cell integration into capillaries in the spheroid-based matrigel plug assay. Because of the selective staining of the endothelium, imaging of larger vessels yielded less favorable results. Using micro-CT or even nano-CT, imaging of capillaries was impossible due to insufficient X-ray absorption and thus insufficient signal-to-noise ratio. Identification of lumen in murine arteries using micro-CT was in contrast superior to UM.
Conclusion: UM and micro-CT are two complementary techniques. Whereas UM is ideal for imaging and especially quantifying capillary networks and arterioles, larger vascular structures are easier and faster to quantify and visualize using micro-CT. 3D information of both techniques is superior to 2D histology. UM and micro-CT together may open a new field of clinical pathology diagnosis.
Wilhelmine Germany enjoyed something of an economic miracle that enabled men from modest backgrounds to become wealthy and influential. Among these was Carl Duisberg, who rose as the son of a modest ribbon weaver in Barmen to head the Bayer chemical works and later the massive German chemical trust I. G. Farben. Like others of his generation, Duisberg was the beneficiary of an excellent scientific education and the opportunities opened up by a rapidly expanding economy. In this massive and definitive biography of the man, Werner Plumpe explores Duisberg’s life as an industrial entrepreneur to uncover the role of the individual manager in the creative-destructive dynamics of capitalism, drawing on his own extensive knowledge of German entrepreneurship and industrial relations in the Wilhelmine and Weimar eras. ...
Child maltreatment remains a major health threat globally that requires the understanding of socioeconomic and cultural contexts to craft effective interventions. However, little is known about research agendas globally and the development of knowledge-producing networks in this field of study. This study aims to explore the bibliometric overview on child maltreatment publications to understand their growth from 1916 to 2018. Data from the Web of Science Core Collection were collected in May 2018. Only research articles and reviews written in the English language were included, with no restrictions by publication date. We analyzed publication years, number of papers, journals, authors, keywords and countries, and presented the countries collaboration and co-occurrence keywords analysis. From 1916 to 2018, 47,090 papers (53.0% in 2010–2018) were published in 9442 journals. Child Abuse & Neglect (2576 papers; 5.5%); Children and Youth Services Review (1130 papers; 2.4%) and Pediatrics (793 papers, 1.7%) published the most papers. The most common research areas were Psychology (16,049 papers, 34.1%), Family Studies (8225 papers, 17.5%), and Social Work (7367 papers, 15.6%). Among 192 countries with research publications, the most prolific countries were the United States (26,367 papers), England (4676 papers), Canada (3282 papers) and Australia (2664 papers). We identified 17 authors who had more than 60 scientific items. The most cited papers (with at least 600 citations) were published in 29 journals, headed by the Journal of the American Medical Association (JAMA) (7 papers) and the Lancet (5 papers). This overview of global research in child maltreatment indicated an increasing trend in this topic, with the world’s leading centers located in the Western countries led by the United States. We called for interdisciplinary research approaches to evaluating and intervening on child maltreatment, with a focus on low-middle income countries (LMICs) settings and specific contexts.
An odonatological survey, based on sighting and photographic documenting, was conducted in Palawan and in Cuyo Island. Ten species were found in Cuyo Island raising the number of known species from five to eleven. There are six additions to the Cuyo Island fauna: Agriocnemis f. femina, Ischnura senegalensis, Pseudagrion microcephalum, Brachydiplax c. chalybea, Neurothemis fluctuans and Neurothemis t. terminata. The occurrence of Coeliccia boettcheri, known from Cuyo, but not recorded during this survey, is discussed in some detail. Forty species were recorded in Palawan. Four new additions to the Palawan fauna were recorded: Lestes p. praemorsus, Pseudagrion microcephalum, Xiphiagrion cyanomelas, and Anax guttatus. Neurobasis daviesi, a rare calopterygid damselfly endemic in Palawan, was encountered at the northern side of Cleopatra Needle during the survey.
I present a new business cycle model in which decision making follows a simple mental process motivated by neuroeconomics. Decision makers first compute the value of two different options and then choose the option that offers the highest value, but with errors. The resulting model is highly tractable and intuitive. A demand function in level replaces the traditional Euler equation. As a result, even liquid consumers can have a large marginal propensity to consume. The interest rate affects consumption through the cost of borrowing and not through intertemporal substitution. I discuss the implications for stimulus policies.