bluuebunny/crossref_metadata_2025_split huggingface dataset:
Durchstarten mit Peptiden
Authors: Mayer Christian 
Published: December 2020

AbstractWie könnte das Leben auf der Erde entstanden sein? Wie könnte es auf fremden erdähnlichen Himmelskörpern entstehen? Um diese Fragen zu beantworten, ist ein Prozess zu ermitteln, der von der Chemie auf der frühen Erde zur Ordnung und Komplexität lebender Systeme führt. Grundlage für eine spontane Evolution könnten peptidbeladene Vesikel sein.
Statt Versuch und Irrtum: Software entwickelt Methoden
Authors: Ehrensberger Christian 
Published: December 2020

AbstractEine HPLC‐Methode für mehrere Analyten zu entwickeln, kostet Zeit. Spezialisierte Softwarepakete können heute die Zahl der erforderlichen Experimente und den Aufwand für die Methodenentwicklung reduzieren. Die Methoden lassen sich robuster gestalten, und die Validität wird für Kontrollbehörden nachvollziehbar dokumentiert.
A two‐step optimization model for the distribution of perishable products
Authors: Gaggero Mauro , Tonelli Flavio 
Published: December 2020

AbstractOptimal planning for distribution networks of perishable products is addressed by means of a two‐step approach pursuing both strategic and tactical goals. The distribution network is represented as a directed graph, and discrete‐time dynamic equations are devised to model the storage and transportation of products. The first decision step consists of an optimization problem to account for a strategic viewpoint. In particular, this problem allows to select optimal values for replenishment cycles of products, safety stocks, and amounts of products to be transferred among the nodes of the network by considering uncertainty on long‐term demand predictions. The second decision step requires the solution of rolling‐horizon optimization problems at the various time buckets that exploit accurate, short‐term predictions of customers' demands according to a tactical perspective. In this case, the strategic decisions on the amounts of products to be transferred are tuned according to the available short‐term predictions of demands. The effectiveness of the proposed approach is showcased by simulations in a case study, in comparison with a classical lot‐for‐lot strategy.
Integrated neuro‐evolution heuristic with sequential quadratic programming for second‐order prediction differential models
Authors: Sabir Zulqurnain , Raja Muhammad Asif Zahoor , Wahab Hafiz Abdul , Shoaib Muhammad , Aguilar J. F. Gómez 
Published: December 2020

AbstractThe current study presents a novel application of integrated intelligent computing solver for numerical treatment of second‐order prediction differential models by exploiting the continuous mapping of artificial neural network (ANN) models of differential operators, global/local search optimization competencies of combined genetic algorithms (GAs) and sequential quadratic programming (SQPs), that is, ANNGASQP. Neural network based differential models are arbitrary integrated to formulate merit function in mean squared error sense and merit function globally optimized with GAs aided with local refinements of SQP. The integrated neuro‐evolutionary ANNGASQP scheme is implemented on four different numerical examples of the prediction differential models for numerical solution to examine the precision, proficiency, and consistency. The comparison of proposed solutions through ANNGASQP for prediction differential models with available reference results indicate the good agreement with absolute errors around 10−6 to 10−8. The worth of ANNGASQP is further established through near optimal values of performance measures on statistical date for multiple trials.
Boosting the Economic Recovery or Closing a Green Deal in Europe? Or Both?
Authors: Valla Natacha 
Published: December 2020

AbstractThe recovery measures announced by Europe in parallel with the Green Deal are the perfect opportunity to step up the effort to measure the impact of public expenditure, both in the short and in the long term. To that aim, it is essential to quickly stabilise benchmarks to measure the financial and non-financial impact of investments in the European recovery plan.
How Hydrogen Admixture Changes Plasma Jet Characteristics in Spray Processes at Low Pressure
Authors: Mauer Georg 
Published: December 2020

AbstractIn plasma spraying, hydrogen is widely used as a secondary working gas besides argon. In particular under low pressure, there are strong effects on the plasma jet characteristics even by small hydrogen percentages. Under such conditions, fundamental mechanisms like diffusion and recombination are affected while this is less relevant under atmospheric conditions. This was investigated for argon–hydrogen mixtures by optical emission spectroscopy (OES). The small electron densities under the investigated low pressure conditions implied specific difficulties in the application of several OES-based methods which are discussed in detail. Adding hydrogen to the plasma gas effected an increased plasma enthalpy. Moreover, the jet expanded radially as the reactive part of the thermal conductivity was enhanced by recombination of atomic hydrogen so that the shock waves were less reflected at the cold jet rims. In the jet cores, the lowest temperatures were found for the highest hydrogen admixture because the energy consumption due to the dissociation of molecular hydrogen outbalanced the increase of the plasma enthalpy. Variations in the radial temperature profiles were related to the jet structure and radial thermal conductivity. The local hydrogen–argon concentration ratios revealed an accumulation of hydrogen atoms at the jet rims. Clear indications were found, that higher hydrogen contents promoted the fast recombination of electrons and ions. However, it is assumed that the transport properties of the plasma were hardly affected by this, since the electron densities and thus the ionization degrees were generally small due to the low pressure conditions.
Striving for Consistency: Why German Sentencing Needs Reform
Authors: Herz Clara 
Published: December 2020

AbstractGiven the debate at the seventy-second Conference of the Association of German Jurists (Deutscher Juristentag) in September 2018 on whether German sentencing needs reform, this Article will explore this very question in greater detail. In this regard, this Article will present various empirical studies in order to demonstrate that notable inconsistencies in German sentencing practice exist. This Article will then point out that broad statutory sentencing ranges, along with fairly vague sentencing guidance, are among the main causes of these disparities. Subsequently, this Article will examine several mechanisms that selected foreign jurisdictions—namely the U.S., the U.K., and Australia—have put in place in order to enhance consistency in their sentencing practices. Three mechanisms of sentencing guidance will be distinguished here: First, formal sentencing guidelines; second, guideline judgments; and third, sentencing advisory bodies as they operate in some Australian states. This Article will compare these mechanisms and assess their merits and drawbacks. Based on this comparative study, this Article will look at how to improve consistency in German sentencing practice. In this respect, this Article will present three steps that German criminal law reform should follow, including a better sentencing framework, the strategic gathering of sentencing data, and the implementation of a flexible sentencing guidelines regime.
Resolving VLBI correlator ambiguity in the time delay model improves precision of geodetic measurements
Authors: Titov O. , Melnikov A. , Lopez Y. 
Published: December 2020

Abstract
The modern Very Long Baseline Interferometry (VLBI) relativistic delay model, as documented in the IERS Conventions, refers to the time epoch when the signal passes one of two stations of an interferometer baseline (selected arbitrarily from the pair of stations and called the ‘reference station’ or ‘station 1’). This model consists of the previous correlation procedure used before the year 2002. However, since 2002 a new correlation procedure that produces the VLBI group delays referring to the time epoch of signal passage at the geocenter has been used. A corresponding correction to the conventional VLBI model delay has to be introduced. However, this correction has not been thoroughly presented in peer reviewed journals, and different approaches are used at the correlators to calculate the final group delays officially published in the IVS database. This may cause an inconsistency up to 6 ps for ground-based VLBI experiments between the group delay obtained by the correlator and the geometrical model delay from the IERS Conventions used in data analysis software. Moreover, a miscalculation of the signal arrival moment to the ‘reference station’ could result in a larger modelling error (up to 50 ps). The paper presents the justification of the correction due to transition between two epochs elaborated from the Lorentz transformation and the approach to model the uncertainty of the calculation of the signal arrival moment. Both changes are particularly essential for upcoming broadband technology geodetic VLBI observations.
Non-economic disciplines still take the back seat: The tale of conflict clauses in investment treaties
Authors: Atanasova Dafina 
Published: December 2020

AbstractThe article offers a new perspective on the interaction of international investment law with other fields of international law based on an empirical study of the use of conflict clauses in over 1,000 investment treaties, providing a first systematic account of this type of provision. The use and content of conflict clauses serve as an indicator of state priorities regarding the coordination of investment standards of protection with other disciplines in the international law matrix. Both numerically and from qualitative perspectives, the clauses’ survey reveals important asymmetries in the engagement on the part of investment treaty makers with international economic disciplines, as compared to non-economic disciplines and human rights more specifically. Indeed, conflict clauses on international economic law are much more common, more detailed and establish clearer priority rules than similar provisions on any other field of international law; and the disparity is only likely to deepen over time. This analysis suggests that negotiators already have the toolkit to create effective links between international norms and institutions, and it is only its use that is uneven. As a result, the article suggests a shift in policy perspective to reflect that reality. Such a shift seems all the more relevant considering the growing body of literature showing that investment arbitrators (and international adjudicators more generally) pay only limited attention to norms from fields beyond their own, thus casting doubt on their capacity to develop a principled approach on the issue without treaty guidance.
How Do Auroral Substorms Depend on Earth's Dipole Magnetic Moment?
Authors: Ebihara Yusuke , Tanaka Takashi 
Published: December 2020

AbstractEarth's dipole magnetic moment M is known to decrease by ∼9% over the past 150 years. It has been argued that the decrease in M makes the near‐Earth space environment different. We investigated how the change in M affects the development of an auroral substorm by increasing and decreasing M by a factor of 1.5 in global magnetohydrodynamics simulation. The ionospheric conductivity decreases with increasing M, in accordance with the aid of empirical relations. When we imposed the southward interplanetary magnetic field, an auroral substorm took place regardless of M, but its development depends largely on M. When M is lower, (1) the expansion onset takes place later, (2) the auroral electrojet develops slowly, and (3) the maximum auroral electrojet increases. The first two consequences are probably associated with the slow magnetospheric convection as manifested by the polar cap potential drop. The third consequence is associated with the nonlinear dependence of substorm‐associated field‐aligned currents (FACs) on the ionospheric conductivity. The maximum values of the westward auroral electrojet and the net FACs increase with decreasing M, whereas the incident magnetic energy into the magnetosphere decreases with decreasing M. This implies that the efficiency of the generation of the substorm‐associated FACs increases with decreasing M. It is also found that, for the lower M‐value, the auroral oval shifts equatorward during the growth phase and expands more equatorward and poleward during the expansion phase. Evolution of substorms depends largely on the value of Earth's dipole moment and the ionospheric conductivity.
Clouds and Radiation Processes in Regional Climate Models Evaluated Using Observations Over the Ice‐free Arctic Ocean
Authors: Inoue Jun , Sato Kazutoshi , Rinke Annette , Cassano John J. , Fettweis Xavier , Heinemann Günther , Matthes Heidrun , Orr Andrew , Phillips Tony , Seefeldt Mark , Solomon Amy , Webster Stuart 
Published: December 2020

AbstractThe presence of clouds in the Arctic regulates the surface energy budget (SEB) over the sea‐ice surface and the ice‐free ocean. Following several previous field campaigns, the cloud‐radiation relationship, including cloud vertical structure and phase, has been elucidated; however, modeling of this relationship has matured slowly. In recognition of the recent decline in the Arctic sea‐ice extent, representation of the cloud system in numerical models should consider the effects of areas covered by sea ice and ice‐free areas. Using an in situ stationary meteorological observation data set obtained over the ice‐free Arctic Ocean by the Japanese Research Vessel Mirai (September 2014), coordinated evaluation of six regional climate models (RCMs) with nine model runs was performed by focusing on clouds and the SEB. The most remarkable findings were as follows: (1) reduced occurrence of unstable stratification with low‐level cloud water in all models in comparison to the observations, (2) significant differences in cloud water representations between single‐ and double‐moment cloud schemes, (3) extensive differences in partitioning of hydrometeors including solid/liquid precipitation, and (4) pronounced lower‐tropospheric air temperature biases. These issues are considered as the main sources of SEB uncertainty over ice‐free areas of the Arctic Ocean. The results from a coupled RCM imply that the SEB is constrained by both the atmosphere and the ocean (and sea ice) with considerable feedback. Coordinated improvement of both stand‐alone atmospheric and coupled RCMs would promote a more comprehensive and improved understanding of the Arctic air‐ice‐sea coupled system.
A novel cancer preventative botanical mixture, TriCurin, inhibits viral transcripts and the growth of W12 cervical cells harbouring extrachromosomal or integrated HPV16 DNA
Authors: Einbond Linda Saxe , Zhou Jing , Wu Hsan-au , Mbazor Emeka , Song Guiyun , Balick Michael , DeVoti James A. , Redenti Stephen , Castellanos Mario R. 
Published: December 2020

Abstract
Background
The phytochemical mixture TriCurin (curcumin, epigallocatechin gallate (EGCG) and resveratrol) eliminates human papillomavirus (HPV) (+) cancer cells in vitro and in vivo. In this study, we further evaluate TriCurin.

Methods
The activity of TriCurin and its individual compounds was assayed on W12 cells, derived from a cervical precancer containing episomal and integrated HPV16 DNA, using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays, microscopy and reverse transcription-polymerase chain reaction (RT-PCR), and on HeLa cells by gene expression analysis. The stability and toxicity of TriCurin microemulsion were tested in an organotypic cervical tissue model.

Results
TriCurin and its individual compounds inhibit the growth of W12 cells, episomal, type 1 and 2 integrants; the relative order of activity is TriCurin, EGCG, curcumin, or resveratrol. RT-PCR shows that TriCurin activates p53 and suppresses HPV16 mRNAs E1, E2, E4, E6 and E7 at 24 h in W12 cells. Gene expression analysis shows that TriCurin activates pro-apoptotic genes and represses anti-apoptotic genes in HeLa cells. TriCurin in a microemulsion is stable and non-toxic to cervical tissue. The combination of TriCurin and tanshinone IIA exhibits additional synergy against HeLa cells.

Conclusions
TriCurin, and the combination of TriCurin with tanshinone IIA, are effective against HPV (+) cells. The phytochemical mixture, in the microemulsion-based cream, is a promising therapeutic for the prevention and treatment of cervical cancer.
Tumour acidosis evaluated in vivo by MRI-CEST pH imaging reveals breast cancer metastatic potential
Authors: Anemone Annasofia , Consolino Lorena , Conti Laura , Irrera Pietro , Hsu Myriam Y. , Villano Daisy , Dastrù Walter , Porporato Paolo E. , Cavallo Federica , Longo Dario Livio 
Published: December 2020

Abstract
Background
Tumour acidosis is considered to play a central role in promoting cancer invasion and migration, but few studies have investigated in vivo how tumour pH correlates with cancer invasion. This study aims to determine in vivo whether tumour acidity is associated with cancer metastatic potential.

Methods
Breast cancer cell lines with different metastatic potentials have been characterised for several markers of aggressiveness and invasiveness. Murine tumour models have been developed and assessed for lung metastases and tumour acidosis has been assessed in vivo by a magnetic resonance imaging-based chemical exchange saturation transfer (CEST) pH imaging approach.

Results
The higher metastatic potential of 4T1 and TS/A primary tumours, in comparison to the less aggressive TUBO and BALB-neuT ones, was confirmed by the highest expression of cancer cell stem markers (CD44+CD24−), highlighting their propensity to migrate and invade, coinciding with the measurement obtained by in vitro assays. MRI-CEST pH imaging successfully discriminated the more aggressive 4T1 and TS/A tumours that displayed a more acidic pH. Moreover, the observed higher tumour acidity was significantly correlated with an increased number of lung metastases.

Conclusions
The findings of this study indicate that the extracellular acidification is associated with the metastatic potential.
RON signalling promotes therapeutic resistance in ESR1 mutant breast cancer
Authors: Dustin Derek , Gu Guowei , Beyer Amanda R. , Herzog Sarah K. , Edwards David G. , Lin Hangqing , Gonzalez Thomas L. , Grimm Sandra L. , Coarfa Cristian , Chan Doug W. , Kim Beom-Jun , De La O Jean-Paul , Ellis Matthew J. , Liu Dan , Li Shunqiang , Welm Alana L. , Fuqua Suzanne A. W. 
Published: December 2020

Abstract
Background
Oestrogen Receptor 1 (ESR1) mutations are frequently acquired in oestrogen receptor (ER)-positive metastatic breast cancer (MBC) patients who were treated with aromatase inhibitors (AI) in the metastatic setting. Acquired ESR1 mutations are associated with poor prognosis and there is a lack of effective therapies that selectively target these cancers.

Methods
We performed a proteomic kinome analysis in ESR1 Y537S mutant cells to identify hyperactivated kinases in ESR1 mutant cells. We validated Recepteur d’Origine Nantais (RON) and PI3K hyperactivity through phospho-immunoblot analysis, organoid growth assays, and in an in vivo patient-derived xenograft (PDX) metastatic model.

Results
We demonstrated that RON was hyperactivated in ESR1 mutant models, and in acquired palbociclib-resistant (PalbR) models. RON and insulin-like growth factor 1 receptor (IGF-1R) interacted as shown through pharmacological and genetic inhibition and were regulated by the mutant ER as demonstrated by reduced phospho-protein expression with endocrine therapies (ET). We show that ET in combination with a RON inhibitor (RONi) decreased ex vivo organoid growth of ESR1 mutant models, and as a monotherapy in PalbR models, demonstrating its therapeutic efficacy. Significantly, ET in combination with the RONi reduced metastasis of an ESR1 Y537S mutant PDX model.

Conclusions
Our results demonstrate that RON/PI3K pathway inhibition may be an effective treatment strategy in ESR1 mutant and PalbR MBC patients. Clinically our data predict that ET resistance mechanisms can also contribute to CDK4/6 inhibitor resistance.
Interleukin-28B dampens protease-induced lung inflammation via IL-25 and TSLP inhibition in epithelial cells
Authors: Yan Bailing , Gao Jinying , Guo Jia , Yang Dong , Li Dan 
Published: December 2020

AbstractAsthma is a chronic respiratory disease with high heterogeneity in human. Different mouse models have been applied for investigation of pathogenesis and treatment of asthma, which target on different cells, receptors and pathways. Interleukin (IL-) 28B, a member of λ-interferons, have been shown to play a protective role in OVA-induced asthma, which is antigen-specific and adaptive immune system dominant. However, the roles of IL-28B in protease-induced asthma, an adaptive immune system independent asthma, are still unclear. Here, we used plant-derived cysteine protease, papain to induce asthma in mice and found that IL-28B was capable of alleviating papain-induced asthma. Papain challenge lead to activation of epithelial cells and production of alarmin, such as IL-25 and thymic stromal lymphopoietin and IL-28B treatment down-regulated their production. Further mechanism was proved to be that IL-28B inhibited the phosphorylation of Erk in epithelial cells via interaction with their receptors. Our results reveal a protective role of IL-28B via regulation of epithelial cells in protease induced asthma.
Cysteic acid grafted to magnetic graphene oxide as a promising recoverable solid acid catalyst for the synthesis of diverse 4H-chromene
Authors: Matloubi Moghaddam Firouz , Eslami Mohammad , Hoda Golfamsadat 
Published: December 2020

Abstract4H-chromenes play a significant role in natural and pharmacological products. Despite continuous advances in the synthesis methodology of these compounds, there is still a lack of a green and efficient method. In this study, we have designed cysteic acid chemically attached to magnetic graphene oxide (MNPs·GO-CysA) as an efficient and reusable solid acid catalyst to synthesize 4H-chromene skeletons via a one-pot three components reaction of an enolizable compound, malononitrile, an aldehyde or isatin, and a mixture of water–ethanol as a green solvent. This new heterogeneous catalyst provides desired products with a good to excellent yield, short time, and mild condition. This procedure presents an environmentally friendly approach for the synthesis of a great number of 4H-chromene derivatives.
Catalytic Asymmetric Osmium-Free Dihydroxylation of Alkenes
Authors: Wang Chuan , Su Shixia 
Published: December 2020

AbstractAsymmetric dihydroxylation of alkenes is one of the cornerstone reactions in organic synthesis, providing a direct entry to optically active vicinal diols, which are not only a subunit in natural products but also versatile building blocks. In recent years, considerable progress in catalytic asymmetric osmium-free dihydroxylation has been achieved. This short review presents a concise summary of the reported methods of catalytic asymmetric osmium-free dihydroxylation.1	Introduction2	Iron-Catalyzed Asymmetric syn-Dihydroxylation of Alkenes3	Manganese-Catalyzed Asymmetric syn-Dihydroxylation of Alkenes4	Palladium/Gold Bimetallic Nanocluster-Catalyzed Asymmetric syn-Dihydroxylation of Alkenes5	Enzyme-Catalyzed Asymmetric anti-Dihydroxylation of Alkenes6	Amine-Catalyzed Asymmetric Formal anti-Dihydroxylation of Enals7	Diselenide-Catalyzed anti-Dihydroxylation of Alkenes8	Molybdenum-Catalyzed Asymmetric anti-Dihydroxylation of Allylic­ Alcohols9	Phase-Transfer-Catalyzed Asymmetric Dihydroxylation of α-Aryl Acrylates10	Conclusion