The Alternative for Germany’s radicalization in historical-comparative perspective

This article chronicles the AfD’s rightward repositioning and compares it with the programmatic development of three postwar German parties on the ideological wings. By highlighting factors that tilt the balance of power away from moderate reformers towards hardliners, this comparative analysis sheds light on the conditions that lead a relatively successful party on the ideological wings, such as the AfD, to radicalize its programme. Four variables stand out: whether party hardliners take the blame for the recent election loss; whether they offer a convincing programmatic and strategic alternative to the reformers; whether changes in party composition strengthen hardliners; and whether external factors enhance their weight within the party. The essay concludes that the AfD’s radicalization was unusual, but not exceptional. It is however too early to conclude that the Federal Republic’s distinctive institutions and political culture no longer impose significant costs on parties that shift their programmes away from the centre

A one-year prospective study of the safety, tolerability and pharmacokinetics of the highest available dose of paliperidone palmitate in patients with schizophrenia

<p>Abstract</p> <p>Background</p> <p>There are no previous reports of paliperidone palmitate's (PP) long term tolerability or pharmacokinetics of the highest dose in patients with schizophrenia. This study evaluates safety and tolerability, as well as pharmacokinetics, of the highest marketed dose of PP (150 mg eq. [234 mg]) in stable patients with schizophrenia over a 1-year period.</p> <p>Methods</p> <p>In this 1-year prospective study, eligible patients (aged 18-65 years; Positive and Negative Syndrome Scale's total score ≤ 70) received an initial deltoid injection of PP 150 mg eq. The second injection one week later and subsequent once-monthly injections were deltoid or gluteal. All injections were to be PP 150 mg eq. Patients willing to participate in intensive pharmacokinetic sampling were classified as Treatment A. Patients unwilling to undergo intensive pharmacokinetic sampling or unable to tolerate the 150 mg eq. dose (consequently receiving flexible doses of 50, 100 or 150 mg eq.) were classified as Treatment B.</p> <p>Results</p> <p>Of the 212 patients (safety analysis set), 73% were men; 45% white; 20% black; 34% Asians; mean (SD) age 41 (10.2) years, and mean (SD) baseline Positive and Negative Syndrome Scale total score 54.9 (9.03). A total of 53% (n = 113) patients completed the study and 104 received PP 150 mg eq. throughout. Mean (SD) mode dose of PP was 144.8 (19.58) mg eq. The dosing initiation regimen resulted in rapidly achieved and maintained therapeutic paliperidone levels over the study (average concentrations during the dosing interval were 34.7, 40.0, and 47.8 ng/mL after the 2nd, 8th, and 14th injection respectively). Most frequent (≥ 10%) treatment-emergent adverse events were nasopharyngitis (n = 37), insomnia (n = 32), injection-site pain (n = 32), headache (n = 28), and tachycardia (n = 27). Akathisia (n = 19) and tremor (n = 11) were the most common extrapyramidal adverse events. 33 patients had an SAE and 27 discontinued due to treatment-emergent adverse events. No deaths were reported. Mean (SD) weight change from baseline was 2.5 (5.41) kg at endpoint. Patients' psychoses remained stable.</p> <p>Conclusions</p> <p>Safety results after one-year therapy with the highest available dose of once-monthly paliperidone palmitate were consistent with results from previous studies, with no new concerns noted. Plasma concentrations were within the expected range.</p> <p>Trial registration no</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01150448">NCT01150448</a></p

Promiscuity in the part-phosphorylative Entner–Doudoroff pathway of the archaeon Sulfolobus solfataricus

AbstractThe hyperthermophilic archaeon Sulfolobus solfataricus metabolises glucose and galactose by a ‘promiscuous’ non-phosphorylative variant of the Entner–Doudoroff pathway, in which a series of enzymes have sufficient substrate promiscuity to permit the metabolism of both sugars. Recently, it has been proposed that the part-phosphorylative Entner–Doudoroff pathway occurs in parallel in S. solfataricus as an alternative route for glucose metabolism. In this report we demonstrate, by in vitro kinetic studies of d-2-keto-3-deoxygluconate (KDG) kinase and KDG aldolase, that the part-phosphorylative pathway in S. solfataricus is also promiscuous for the metabolism of both glucose and galactose

Low-temperature mechanical dissipation of thermally evaporated indium film for use in interferometric gravitational wave detectors

Indium bonding is under consideration for use in the construction of cryogenic mirror suspensions in future gravitational wave detectors. This paper presents measurements of the mechanical loss of a thermally evaporated indium film over a broad range of frequencies and temperatures. It provides an estimate of the resulting thermal noise at 20 K for a typical test mass geometry for a cryogenic interferometric gravitational wave detector from an indium layer between suspension elements

Structure of a bifunctional alcohol dehydrogenase involved in bioethanol generation in <em>Geobacillus thermoglucosidasius </em>

Bifunctional alcohol/aldehyde dehydrogenase (ADHE) enzymes are found within many fermentative microorganisms. They catalyse the conversion of an acyl-coenzyme A to an alcoholviaan aldehyde intermediate; this is coupled to the oxidation of two NADH molecules to maintain the NAD+pool during fermentative metabolism. The structure of the alcohol dehydrogenase (ADH) domain of an ADHE protein from the ethanol-producing thermophileGeobacillus thermoglucosidasiushas been determined to 2.5 Å resolution. This is the first structure to be reported for such a domain.In silicomodelling has been carried out to generate a homology model of the aldehyde dehydrogenase domain, and this was subsequently docked with the ADH-domain structure to model the structure of the complete ADHE protein. This model suggests, for the first time, a structural mechanism for the formation of the large multimeric assemblies or `spirosomes' that are observed for this ADHE protein and which have previously been reported for ADHEs from other organisms.</jats:p

Antibiotic resistance patterns in soils across the Scottish landscape

The environment disseminates antimicrobial-resistance genes; however, it remains challenging to distinguish whether human activities exacerbate antimicrobial resistance or what is natural. Here, we quantified ~300 resistance-related genes in 200+ Scottish soil samples. Location or land use does not explain gene differences, but nutrient levels reduce gene richness. Elevated levels of metals increased gene richness, and selenium increased transposase levels. Rainfall and persistent organic pollutants also increased transposase relative abundance, possibly promoting conditions conducive to the horizontal transfer of antimicrobial-resistance genes. Selenium and polychlorinated biphenyls were primary factors in gene abundance, while polychlorinated biphenyls, polycyclic aromatic hydrocarbons, and pH influenced gene diversity. Polychlorinated biphenyls are derived from anthropogenic activities, highlighting human activities’ potential impact on gene prevalence. This is the first national-scale, high spatial resolution dataset of antimicrobial-resistance genes in Scottish soils and provides a novel resource on which to build future studies

Coatings and surface treatments for enhanced performance suspensions for future gravitational wave detectors

Further improvements in the low frequency sensitivity of gravitational wave detectors are important for increasing the observable population of astrophysical sources, such as intermediate mass compact black hole binary systems. Improvements in the lower stage mirror and suspension systems will set challenging targets for the required thermal noise performance of the cantilever blade springs, which provide vertical softness and, thus, isolation to the mirror suspension stack. This is required due to the coupling between the vertical and horizontal axes due to the curvature of the Earth. This can be achieved through use of high mechanical Q materials, which are compatible with cryogenic cooling, such as crystalline silicon. However, such materials are brittle, posing further challenges for assembly/jointing and, more generally, for long-term robustness. Here, we report on experimental studies of the breaking strength of silicon at room temperature, via both tensile and 4-point flexural testing; and on the effects of various surface treatments and coatings on durability and strength. Single- and multi-layer DLC (diamond-like carbon) coatings, together with magnetron-sputtered silica and thermally-grown silica, are investigated, as are the effects of substrate preparation and argon plasma pre-treatment. Application of single- or multi-layer DLC coatings can significantly improve the failure stress of silicon flexures, in addition to improved robustness for handling (assessed through abrasion tests). Improvements of up to 80% in tensile strength, a twofold increase in flexural strength, in addition to a 6.4 times reduction in the vertical thermal noise contribution of the suspension stack at 10 Hz are reported (compared to current Advanced LIGO design). The use of silicon blade springs would also significantly reduce potential 'crackling noise' associated with the underlying discrete events associated with plastic deformation in loaded flexures