bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic engineering approaches for the fermentative production of phenylglycines
Authors: Moosmann David , Mokeev Vladislav , Kulik Andreas , Osipenkov Natalie , Kocadinc Susann , Ort-Winklbauer Regina , Handel Franziska , Hennrich Oliver , Youn Jung-Won , Sprenger Georg A. , Mast Yvonne 
Published: February 2020

AbstractL-phenylglycine (L-Phg) is a rare non-proteinogenic amino acid, which only occurs in some natural compounds, such as the streptogramin antibiotics pristinamycin I and virginiamycin S or the bicyclic peptide antibiotic dityromycin. Industrially, more interesting than L-Phg is the enantiomeric D-Phg as it plays an important role in the fine chemical industry, where it is used as a precursor for the production of semisynthetic β-lactam antibiotics. Based on the natural L-Phg operon from Streptomyces pristinaespiralis and the stereo-inverting aminotransferase gene hpgAT from Pseudomonas putida, an artificial D-Phg operon was constructed. The natural L-Phg operon, as well as the artificial D-Phg operon, was heterologously expressed in different actinomycetal host strains, which led to the successful production of Phg. By rational genetic engineering of the optimal producer strains S. pristinaespiralis and Streptomyces lividans, Phg production could be improved significantly. Here, we report on the development of a synthetic biology-derived D-Phg pathway and the optimization of fermentative Phg production in actinomycetes by genetic engineering approaches. Our data illustrate a promising alternative for the production of Phgs.
Hemophagocytic lymphohistiocytosis in adults: collaborative analysis of 137 cases of a nationwide German registry
Authors: Birndt Sebastian , Schenk Thomas , Heinevetter Babett , Brunkhorst Frank M. , Maschmeyer Georg , Rothmann Frank , Weber Thomas , Müller Markus , Panse Jens , Penack Olaf , Schroers Roland , Braess Jan , Frickhofen Norbert , Ehl Stephan , Janka Gritta , Lehmberg Kai , Pletz Mathias W. , Hochhaus Andreas , Ernst Thomas , La Rosée Paul 
Published: February 2020

Abstract
Purpose
Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome emerging from a deregulated immune response due to various triggers. In adults, systematic data are sparse, which is why recommendations on diagnosis and management have been adopted from pediatric guidelines. A nationwide clinical registry with associated consulting service as collaborative initiative of HLH-specialized pediatricians and hematologists was initiated to better characterize HLH in adults.

Methods
Patients with proven or suspected HLH were registered by 44 institutions. Both HLH-2004 diagnostic criteria and the HScore (www.saintantoine.aphp.fr/score/) were used to confirm HLH diagnosis. Data referring to underlying disease, treatment, outcome, clinical presentation and laboratory findings were recorded.

Results
The study included 137 patients and provides the first systematic data on adult HLH in Germany. Median age was 50 years with a wide range (17–87 years), 87 patients (63.5%) were male. Most common triggering diseases were infections in 61 patients (44.5%) and malignancies in 48 patients (35%). Virtually all patients had elevated ferritin concentrations, and 74% had peak concentrations greater than 10,000 µg/l. At time of analysis, 67 of 131 patients (51%) had died. Patients with malignancy-associated HLH had the shortest median survival (160 days), however no statistically significant difference between subgroups was observed (p = 0.077). Platelets under 20*109/l and low albumin concentrations (< 20 g/l) were associated with poor overall and 30-day survival.

Conclusion
Close multidisciplinary case consultation and cooperation is mandatory when treating adult HLH patients. Early contact with reference centers is recommended, especially in relapsing or refractory disease.
Plattformbasiertes Sharing und Pooling im Verkehrssektor — ein Systematisierungsansatz
Authors: Viergutz Kathrin , Maertens Sven , Scheier Benedikt , Lütjens Klaus , Goletz Mirko , Grimme Wolfgang , Liedtke Gernot 
Published: February 2020

ZusammenfassungIm Verkehrssektor manifestiert sich die Digitalisierung zunehmend durch plattformbasierte Geschäftsmodelle, die Mobilitätsdienstleistungen vermitteln. Auf diese Weise entsteht die Möglichkeit, Fahrten und Fahrzeuge mit anderen, meist fremden Mitreisenden zu teilen. Durch Suchfunktionen und Matchmaking können attraktive Angebote mit hoher Dienstleistungsqualität „on demand“ aufgebaut werden, die eine stärkere Individualisierung der Mobilität als der noch weitgehend starre Nahverkehr ermöglichen.
Was die Wirtschaftspolitik vom Wirtschaftsnobelpreis des Jahres 2019 lernen kann
Authors: Menkhoff Lukas , Seitz Helke 
Published: February 2020

ZusammenfassungAbhijit Banerjee, Esther Duflo und Michael Kremer sind 2019 mit dem Wirtschaftsnobelpreis geehrt worden. Dies vor allem für ihren experimentellen Ansatz zur Linderung der weltweiten Armut. Die Laureaten nutzen randomisierte Experimente, um entwicklungspolitische Maßnahmen zu evaluieren. So haben sie die Grenzen der in Indien genutzten Mikrofinanzierung aufgezeigt. Zwar gibt es durchaus Kritik an dieser mikroökonomisch ausgerichteten Forschung. Die gründliche Evaluierung von politischen Maßnahmen — wie beispielsweise in der evidenzbasierten Wirtschaftspolitik — sollte aber ein gemeinsames Ziel von Wissenschaft und Politik werden.
EU-US trade post-trump perspectives: TTIP aspects related to foreign direct investment and innovation
Authors: Jungmittag Andre , Welfens Paul J. J. 
Published: February 2020

AbstractThe international economic debate on the Transatlantic Trade and Investment Partnership (TTIP) has focused mainly on trade induced real income gains while the Foreign Direct Investment (FDI)-related and innovation induced benefits have been largely neglected, although the EU and the US are leading FDI host countries and FDI source countries. Moreover, from a theoretical perspective a knowledge production function has to be considered in order to analyze FDI and innovation dynamics – and this can then be linked to output and economic growth, respectively. It is argued that such a Schumpeterian approach for an open economy is needed to understand deep integration dynamics while the standard CGE model used by Francois et al. (2013) leads to an underestimation of deep integration projects such as TTIP. The panel data estimation of knowledge production functions for 20 EU countries between 2002 and 2012 shows clear empirical evidence that a rise of the number of researchers and of the FDI stock-GDP ratio (or related variables) will raise patent applications. Additionally, a higher per capita income – that could reflect trade related real income gains in the context of TTIP – also contributes to new knowledge and a fortiori to higher GDP. Time series data analysis for Germany indicates additionally that FDI induced higher innovation dynamics will raise output - combining trade benefits and FDI/innovation related real income gains plus transatlantic macroeconomic interdependency effects a real income gain of nearly 2% should be expected for Germany (and the EU). As the Trump Administration is focusing on bilateralism, the US is essentially renouncing a considerable output increase and opportunities to improve its current account; instead the Trump Administration has adopted a policy of protectionism which is likely to undermine trade dynamics and economic growth. In the long run, transatlantic trade perspectives could improve.
Coronary plaque tissue characterization in patients with premature coronary artery disease
Authors: Xie Jianchang , Qi Jie , Mao Hengyi , Wang Ningfu , Ye Xianhua , Zhou Liang , Tong Guoxin , Yang Jianmin , Pan Hao , Huang Jinyu 
Published: February 2020

AbstractPremature coronary artery disease (CAD) studies rarely involve coronary plaque characterization. We characterize coronary plaque tissue by radiofrequency intravascular ultrasound (IVUS) in patients with premature CAD. From July 2015 to December 2017, 220 patients from the Department of Cardiology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine with first occurrence of angina or myocardial infarction within 3 months were enrolled. Patients with premature CAD (n = 47, males aged < 55 years, and females aged < 65 years) or later CAD (n = 155) were retrospectively compared for cardiovascular risk factors, laboratory examination findings, coronary angiography data, gray-scale IVUS, and iMap-IVUS. The mean age was 53.53 ± 7.24 vs. 70.48 ± 8.74 years (p < 0.001). The groups were similar for traditional coronary risk factors except homocysteine (18.60 ± 5.15 vs. 17.08 ± 4.27 µmol/L, p = 0.043). After matching for baseline characteristics, LDL cholesterol (LDL-C) was higher for premature CAD than later CAD (2.50 ± 0.96 vs. 2.17 ± 0.80 mmol/L, p = 0.019). Before the matching procedure, the premature CAD group had shorter target lesion length [18.50 (12.60–32.00) vs. 27.90 (18.70–37.40) mm, p = 0.002], less plaque volume [175.59 (96.60–240.50) vs. 214.73 (139.74–330.00) mm3, p = 0.013] than the later CAD group. After the matching procedure, the premature CAD group appeared to be less plaque burden (72.69 ± 9.99 vs. 74.85 ± 9.80%, p = 0.005), and positive remodeling (1.03 ± 0.12 vs. 0.94 ± 0.18, p = 0.034), and lower high risk feature incidence (p = 0.006) than the later CAD group. At the plaque’s minimum lumen, premature CAD had more fibrotic (p < 0.001), less necrotic (p = 0.001) and less calcified areas (p = 0.012). Coronary plaque tissue was more fibrotic with less necrotic and calcified components in premature than in later CAD, and the range and degree of atherosclerosis were significantly lower.
The decomposition-based outer approximation algorithm for convex mixed-integer nonlinear programming
Authors: Muts Pavlo , Nowak Ivo , Hendrix Eligius M. T. 
Published: February 2020

AbstractThis paper presents a new two-phase method for solving convex mixed-integer nonlinear programming (MINLP) problems, called Decomposition-based Outer Approximation Algorithm (DECOA). In the first phase, a sequence of linear integer relaxed sub-problems (LP phase) is solved in order to rapidly generate a good linear relaxation of the original MINLP problem. In the second phase, the algorithm solves a sequence of mixed integer linear programming sub-problems (MIP phase). In both phases the outer approximation is improved iteratively by adding new supporting hyperplanes by solving many easier sub-problems in parallel. DECOA is implemented as a part of Decogo (Decomposition-based Global Optimizer), a parallel decomposition-based MINLP solver implemented in Python and Pyomo. Preliminary numerical results based on 70 convex MINLP instances up to 2700 variables show that due to the generated cuts in the LP phase, on average only 2–3 MIP problems have to be solved in the MIP phase.
Drug-related problems and pharmacy interventions in non-prescription medication, with a focus on high-risk over-the-counter medications
Authors: Ylä-Rautio Hanna , Siissalo Sanna , Leikola Saija 
Published: February 2020

AbstractBackground The risks associated with over-the-counter medication are often underestimated by consumers. The incorrect use of certain medications can lead to significant patient harm. Inappropriate use can be prevented by pharmaceutical counselling. Objective To determine the number and nature of drug-related problems in over-the-counter medication with a special emphasis on high-risk over-the-counter medications. Setting Fifty-two community pharmacies in Finland. Method This observational study was conducted as a questionnaire survey. The pharmacists working in participating pharmacies documented the observed drug-related problems and pharmacy interventions in over-the-counter medication during 1 week using an electronic study form based on the Westerlund drug-related problem classification system. Main outcome measure The prevalence of drug-related problems and problem types in different medication categories. Results The 52 community pharmacies documented 339 drug-related problems in 0.6% of over-the-counter customers, the most common problem being “Uncertainty about the indication for the drug” (39.2%). A significant proportion of the documented problems (26.3%) concerned high-risk over-the-counter medications, and the majority of these cases were associated with non-steroidal anti-inflammatory drugs (21.8%). In total, pharmacies made 641 interventions to resolve the drug-related problems. For majority of drug-related problems (87%), pharmacist’s intervention involved counselling. In more than half of the problem cases, the pharmacy intervention was precautionary. Conclusion Pharmacists intervene in and prevent problems related to over-the-counter medications, including high-risk medications like analgesics, in which inappropriate use due to consumers’ lack of knowledge can lead to severe consequences. As the selection and use of over-the-counter medications is continuously increasing, pharmaceutical counselling should be readily available and actively provided for consumers to achieve safer self-medication.
Catalytic synthesis of bioactive 2H-chromene alcohols from (−)-isopulegol and acetone on sulfonated clays
Authors: Laluc Mathias , Mäki-Arvela Päivi , Peixoto Andreia F. , Li-Zhulanov Nikolai , Sandberg Thomas , Salakhutdinov Nariman F. , Volcho Konstantin , Freire Cristina , Sidorenko Alexander Yu. , Murzin Dmitry Yu. 
Published: February 2020

AbstractCondensation of (−)-isopulegol with acetone was investigated at 25–40 °C over clay based materials (K10, cloisite Na+ and halloysite nanotubes) modified with sulfonic acid groups by one-pot sulfonation with chlorosulfonic acid or via organosilylation with 2-(4-chlrosulfonylphenyl)-ethyltrimethoxysilane. The target product was the R diastereomer of dimethyl-substituted octahydro-2H-chromen-4-ol with exhibits antiviral activity. The catalysts were characterized by a range of physico-chemical methods. The effect of the initial isopulegol concentrations on the yield of ketone-derived chromenols and the R/S isomers ratio was studied for the first time. The best catalyst was a highly acidic, large pore K10-clay modified by sulfonic acid. Varying the initial concentration of the reagents allows to find a balance between dehydration by-products and a side etherification reaction. A high yield (73%) of the desired chromenols was reached using 0.52 mol/l initial (−)-isopulegol concentration after 240 min at 87% substrate conversion and reaction temperature 25 °C. The yield exceeded that of other previously reported in the open literature catalysts.
Biomarker responses and accumulation of polycyclic aromatic hydrocarbons in Mytilus trossulus and Gammarus oceanicus during exposure to crude oil
Authors: Turja Raisa , Sanni Steinar , Stankevičiūtė Milda , Butrimavičienė Laura , Devier Marie-Hélène , Budzinski Hélène , Lehtonen Kari K. 
Published: February 2020

AbstractIn the brackish water Baltic Sea, oil pollution is an ever-present and significant environmental threat mainly due to the continuously increasing volume of oil transport in the area. In this study, effects of exposure to crude oil on two common Baltic Sea species, the musselMytilus trossulusand the amphipodGammarus oceanicus, were investigated. The species were exposed for various time periods (M. trossulus4, 7, and 14 days,G. oceanicus4 and 11 days) to three oil concentrations (0.003, 0.04, and 0.30 mg L−1based on water measurements, nominally aimed at 0.015, 0.120, and 0.750 mg L−1) obtained by mechanical dispersion (oil droplets). Biological effects of oil exposure were examined using a battery of biomarkers consisting of enzymes of the antioxidant defense system (ADS), lipid peroxidation, phase II detoxification (glutathioneS-transferase), neurotoxicity (acetylcholinesterase inhibition), and geno- and cytotoxicity (micronuclei and other nuclear deformities). In mussels, the results on biomarker responses were examined in connection with data on the tissue accumulation of polycyclic aromatic hydrocarbons (PAH). InM. trossulus, during the first 4 days of exposure the accumulation of all PAHs in the two highest exposure concentrations was high and was thereafter reduced significantly. Significant increase in ADS responses was observed inM. trossulusat 4 and 7 days of exposure. At day 14, significantly elevated levels of geno- and cytotoxicity were detected in mussels. InG. oceanicus, the ADS responses followed a similar pattern to those recorded inM. trossulusat day 4; however, inG. oceanicus, the elevated ADS response was still maintained at day 11. Conclusively, the results obtained show marked biomarker responses in both study species under conceivable, environmentally realistic oil-in-seawater concentrations during an oil spill, and in mussels, they are related to the observed tissue accumulation of oil-derived compounds.
Cooperative effect of cobalt and zeolite in controlling activity and stability of a catalytic Fischer–Tropsch process
Authors: Sineva Liliya V. , Asalieva Ekaterina Yu. , Kulchakovskaya Ekaterina V. , Gryaznov Kirill O. , Mordkovich Vladimir Z. 
Published: February 2020

AbstractThe use of zeolites in Co-catalysts of Fischer–Tropsch synthesis (FTS) results in cooperative effect in the form of sudden increase of the zeolite activity in catalysing secondary transformations of FTS-generated hydrocarbons at unusually low temperatures in the range of 170–260 °C. In addition, hydrophobic zeolites in H-form allow changing the hydrophobicity of the pore walls and influence capillary condensation phenomena for intermediate species. The most unexpected effect of Co and hydrophobic zeolites is the improvement of degradation behaviour of the catalysts due to involvement of FTS-generated water into formation of additional Bronsted centres thus preventing undesirable oxidation of heat-conductive metal additives and other water-induced degradation processes. In addition, the stability of catalyst behaviour and its lifetime increase.
Thymoquinone-loaded ethosome with breast cancer potential: optimization, in vitro and biological assessment
Authors: Nasri Shilan , Ebrahimi-Hosseinzadeh Bahman , Rahaie Mahdi , Hatamian-Zarmi Ashrafalsadat , Sahraeian Razi 
Published: February 2020

Abstract
Ethosomes are most commonly used vesicular delivery system compared to other lipidic vesicles due to its ethanolic content. Thymoquinone (TQ), the main biologically active complex of Black Cumin seed, has established anticancer activities in several tumors. In this work, the preparation of ethosome for TQ encapsulation by response surface method (RSM) was developed. Central composite design (CCD) was used to optimize three effective parameters involved in ethosome structure including phospholipid, cholesterol and ethanol concentration and the combined effects of them, as well. The obtained optimum values for the variables were phospholipid 5% (W/W), ethanol 45% (V/V) and cholesterol 1.5% (W/W) which were validated by experimental assay. The ethosomal formulation was more characterized for vesicle shape, size, zeta potential and entrapment efficiency percentage. The result showed an efficiency of 99% for drug entrapment with average vesicle size and zeta potential of 20 ± 1 nm and − 63 ± 2 mv, respectively. A quadratic model with a high adequacy (R2) for size and zeta potential of 0.9319 and 0.9338, respectively, was resulted from RSM and experimental assay. Thymoquinone (TQ) encapsulated in optimized ethosome. Also, cellular toxicity and release test was done. The toxicity and release curves were obtained and the cytotoxic activity of the ethosomic TQ against MCF-7 cell lines was greater than free TQ. IC50 values of free TQ, ethosomic TQ, were found to be 1.10 µg/ml, 0.95 µg/ml, respectively. The generated model suggests a new approach to prediction and experimental lipidic carriers.

Graphic abstract

Central composite design (CCD) was used to optimize three effective parameters involved in ethosome structure including phospholipid, cholesterol and ethanol concentration and the combined effects of them, as well. The ethosomal formulation was more characterized for vesicle shape, size, zeta potential and entrapment efficiency percentage. Also, cellular toxicity and release test was done. The toxicity and release curves were obtained and the cytotoxic activity of the ethosomic TQ against MCF-7 cell lines was greater than free TQ.
The Effects of Rotary Degassing Treatments on the Melt Quality of an Al–Si Casting Alloy
Authors: Gyarmati Gábor , Fegyverneki György , Tokár Monika , Mende Tamás 
Published: February 2020

AbstractIn order to produce cast components, which meet the quality requirements of the automotive and aerospace industries, the control of liquid metal quality prior to the casting process is essential. Rotary degassing is the most commonly used melt treatment method in the foundry industry, which can effectively reduce the inclusion and solute hydrogen content of the metal. This procedure is often combined with fluxing, which allows more efficient inclusion removal during melt processing. In this study, the effects of rotary degassing treatments executed with and without flux addition on the melt cleanliness were compared. The quality of the molten metal was characterized by the microscopic inspection of K-mold specimens, X-ray computed tomography of reduced pressure test samples, and by Density-Index evaluation. The inclusions found on the fracture surfaces of K-mold samples were analyzed with energy-dispersive X-ray spectroscopy. Based on the results, rotary degassing coupled with flux addition can be an effective inclusion and solute hydrogen removal technique that can significantly improve melt quality. On the other hand, rotary degassing executed without flux addition can increase the inclusion content of the melts. This can be attributed to the chemical reaction between the liquid alloy and the N2 purging gas during the degassing process. It was also found that inclusion content highly influences the tendency to porosity formation.
Laser powder bed fusion of Nd–Fe–B permanent magnets
Authors: Bittner Florian , Thielsch Juliane , Drossel Welf-Guntram 
Published: February 2020

AbstractIn this work, we use laser powder bed fusion (LPBF) to produce Nd–Fe–B magnets. A suitable process window is developed, which allows to fabricate isotropic samples with outstanding magnetic performance. The sample quality is mainly defined by the energy input during LPBF and sintering or delamination occurs, if the process parameter are improperly adjusted. Magnetic and structural properties become better as energy input increases, until the material-specific limit for processability has been reached. Magnets with coercivity of 886 kA/m (µ0Hc = 1.1 T) and maximum energy product of 63 kJ/m3 can be produced from Nd-lean commercial powder without any post treatment. Thereby, our samples represent the new benchmark for permanent magnets produced by additive manufacturing. On the example of coercivity, the impact of laser power, scan velocity and hatch spacing is discussed. It is shown that coercivity can be sufficiently well described by a simple phenomenological model.