bluuebunny/crossref_metadata_2025 huggingface dataset:
Fluoride Evaporation and Melting Characteristics of CaF2–CaO–Al2O3–MgO–Li2O–(TiO2) Slag for Electroslag Remelting
Authors: Ju Jian-tao , Ji Guang-heng , Tang Chen-mei , An Jia-liang
Published: June 2020

This study presents the evaporation mechanism of fluoride from CaF2–CaO–Al2O3–MgO–Li2O–(TiO2) slag and their melting characteristics at different TiO2 contents by thermogravimetric analysis and melting‐temperature‐characteristic testing. FactSage is used to identify the major components evaporating from the tested slags. The results show that the slag melting point decreases with an increase in the TiO2 content. In addition, X‐ray diffraction analysis reveal that with an increase in the TiO2 content, the total CaF2 and Ca12Al14F2O32 content increase while the MgAl2O4 content decrease. The gaseous species easily evaporating from slags, including LiF and CaF2, are the primary contributors to fluoride loss. The apparent activation energy for LiF evaporation is calculated to be in the range of 116.75–227.62 kJ mol−1 and this process can be described as 3D diffusion. In the case of CaF2 evaporation, the apparent activation energy is calculated to be in the range of 365.98–492.33 kJ mol−1 and this process followed the mechanism of random nucleation and growth.
Purified Starches from 18 Pulses Have Markedly Different Morphology, Oil Absorption and Water Absorption Capacities, Swelling Power, and Turbidity
Authors: Sangokunle Oluwatoyin O. , Sathe Shridhar K. , Singh Prashant
Published: June 2020

Pulse starch is a promising alternative food ingredient. The demand for pulse starch is increasing due to attributed functionalities, healthier food preferences, and its clean label. However, the functional attributes that would facilitate utilization of pulse starch by food industries require additional investigation. In this study, starch from 18 pulses are purified and selected functional properties are characterized. 18‐pulse seed types are wet milled and used for starch isolation. Yield, proximate compositions, solubility, swelling power, least gelation concentration, oil and water absorption capacities (OAC and WAC), and water absorption and solubility indexes (WAI and WSI) are characterized for each of the starches. Additionally, the effect of moist‐heat treatment and oil‐type on WAC, WAI, WSI, and OAC are determined. Results indicate differences in yield, proximate composition, L* color value, granule morphology, and starch WAC and OAC based on biotypes and significantly (p < 0.05) differed by moist‐heat treatment, and oil type, respectively. The WAC is correlated to amylose content (Pearson correlation coefficient; r = 0.551, p < 0.01). This study provides a basis for better understanding the functionality of pulse starches, enabling their improved usage as food ingredients.
Study of a new type of self‐centering beam‐column joint in steel frame structures
Authors: Jiang Huanjun , Bu Haifeng , He Liusheng
Published: June 2020

A new type of self‐centering beam‐column joint with installed steel arc plates is proposed in this study. First, mechanical behavior of the self‐centering joint using prestressed steel strands to provide the centering force is theoretically analyzed in detail, followed by experimental validation. New joints with different arc plate parameters are designed and tested under cyclic loading. Test results show that the hysteretic curve of the new joint exhibits typical characteristic of self‐centering capacity. By parametric analysis of five design parameters of the arc plate, it is found that vector height has the greatest influence on the joint's moment‐rotation skeleton curve, which is consistent with experimental findings. A simplified model of the joint is built in OpenSees to simulate its hysteretic behavior, which agrees well with the tested results. To demonstrate the effectiveness of the new joint to improve the seismic performance of the overall structure, a series of nonlinear time history analysis on a steel frame structure with the new joint under earthquakes are conducted, which show that the joint is particularly effective in reducing the residual interstory drift response.
Darcy‐Brinkman flow through a slider bearing with surface roughnesses
Authors: Faltas M.S. , Sherief H.H. , Mansour M.A.
Published: June 2020

A double perturbation analysis is performed to the Darcy–Brinkman equations for a two‐dimensional slider bearing with homogeneous surface roughness. The surface roughness is parallel to the flow direction. The stationary random model is used to mimic the surface roughness of the slider bearing walls. The slider is filled with a porous medium. The effect of the corrugations on the average load capacity is examined as function of wave length and the permeability of the slider bearing. The limiting cases of Stokes and Darcy's flows are discussed.
Dynamic intensity factors for multiple permeable cracks in piezoelectric materials
Authors: Liu Hai‐Tao
Published: June 2020

This article presents the dynamic intensity factors for multiple permeable Mode‐I cracks in piezoelectric materials plane by means of the generalized Almansi's theorem. The Fourier transform is used and the present problem is formulated into two pairs of dual integral equations. The dual integral equations are solved by the Schmidt method. The dynamic stress intensity factors (DSIFs) and the dynamic electric displacement intensity factor (DEDIF) at the crack tips are given. It is shown that the effects of the crack length, the distance between two parallel cracks and the circular frequency of incident wave near the crack tips on the DSIFs and DEDIF.
Sparse basis pursuit for compliance minimization in the vanishing volume ratio limit
Authors: Evgrafov Anton , Sigmund Ole
Published: June 2020

We consider a non‐smooth convex variational problem appearing as a formal limit of compliance minimization in the vanishing volume ratio limit. The problem has a classical basis pursuit form, and several successful algorithms have been utilized to solve problems of this class in other application contexts. We discuss the well‐posedness and regularity of solutions to these problems, possible solution algorithms, and their discretizations as relevant in this mechanical engineering context. We then test the algorithms on a few benchmark problems with available analytical solutions.

We find that whereas many algorithms are successful in estimating the optimal objective value to the problem to a high accuracy, the same cannot be said about finding the optimal solutions themselves. In particular, in some examples the algorithms struggle to properly identify the areas where the solutions should vanish entirely. We also discuss an example where the found optimal solutions are not sparse even though sparse(r) solutions exist.
The cortical oscillatory patterns associated with varying levels of reward during an effortful vigilance task
Authors: Byrne Adam , Kokmotou Katerina , Roberts Hannah , Soto Vicente , Tyson-Carr John , Hewitt Danielle , Giesbrecht Timo , Stancak Andrej
Published: June 2020

We explored how reward and value of effort shapes performance in a sustained vigilance, reaction time (RT) task. It was posited that reward and value would hasten RTs and increase cognitive effort by boosting activation in the sensorimotor cortex and inhibition in the frontal cortex, similar to the horse-race model of motor actions. Participants performed a series of speeded responses while expecting differing monetary rewards (0 pence (p), 1 p, and 10 p) if they responded faster than their median RT. Amplitudes of cortical alpha, beta, and theta oscillations were analysed using the event-related desynchronization method. In experiment 1 (N = 29, with 12 females), reward was consistent within block, while in experiment 2 (N = 17, with 12 females), reward amount was displayed before each trial. Each experiment evaluated the baseline amplitude of cortical oscillations differently. The value of effort was evaluated using a cognitive effort discounting task (COGED). In both experiments, RTs decreased significantly with higher rewards. Reward level sharpened the increased amplitudes of beta oscillations during fast responses in experiment 1. In experiment 2, reward decreased the amplitudes of beta oscillations in the ipsilateral sensorimotor cortex. Individual effort values did not significantly correlate with oscillatory changes in either experiment. Results suggest that reward level and response speed interacted with the task- and baseline-dependent patterns of cortical inhibition in the frontal cortex and with activation in the sensorimotor cortex during the period of motor preparation in a sustained vigilance task. However, neither the shortening of RT with increasing reward nor the value of effort correlated with oscillatory changes. This implies that amplitudes of cortical oscillations may shape upcoming motor responses but do not translate higher-order motivational factors into motor performance.
Abdominal lymph node size in children at computed tomography
Authors: Spijkers Suzanne , Staats Judith M. , Littooij Annemieke S. , Nievelstein Rutger A. J.
Published: June 2020

Background

Lymph node enlargement is commonly used to indicate abnormality.

Objective

To evaluate the normal size and prevalence of abdominal lymph nodes in children at CT.

Materials and methods

In this retrospective study, we included a total of 152 children ages 1–17 years who underwent abdominal CT examination after high-energy trauma. We measured abdominal lymph nodes in five lymph node stations (inguinal, iliac, para-aortic, hepatic and mesenteric). For the largest lymph node in each level, we measured long- and short-axis diameters in both the axial and coronal planes. We then calculated distribution parameters, correlation coefficients between lymph node size and age, and reference intervals.

Results

The prevalence of detectable lymph nodes was high for the inguinal (100%), iliac (98%), para-aortic (97%) and mesenteric (99%) stations and lower for the hepatic station (32%). Lymph node size showed small to medium significant correlations (ranging from 0.21 to 0.50) with age. When applying the Lugano criteria and RECIST (Response Criteria in Solid Tumors), 29 children (19%) would have had one or more enlarged abdominal lymph nodes.

Conclusion

The results of this study provide normative data of abdominal lymph node size in children. The current adult guidelines for enlarged lymph nodes seem adequate for most children with the exception of young adolescents, in which larger lymph nodes were relatively common, particularly in the inguinal region.
Micro-environmental cross-talk in an organotypic human melanoma-in-skin model directs M2-like monocyte differentiation via IL-10
Authors: Michielon Elisabetta , López González Marta , Burm Judith L. A. , Waaijman Taco , Jordanova Ekaterina S. , de Gruijl Tanja D. , Gibbs Susan
Published: June 2020

Preclinical assessment of novel therapies to fight cancer requires models that reflect the human physiology and immune response. Here, we established an in vitro three-dimensional (3D) reconstructed organotypic human melanoma-in-skin (Mel-RhS) model to investigate cellular and molecular features of tumor formation over a period of 6 weeks. Tumor nests developed over time at the epidermal–dermal junction and spread towards the dermis, in places disrupting the basement membrane. This coincided with secretion of matrix metalloproteinase 9 (MMP-9) by melanoma cells. These features resemble the initial stages of invasive melanoma. Interestingly, while the SK-MEL-28 cell line did not secrete detectable levels of interleukin-10 (IL-10) in traditional two-dimensional monolayers, it did express IL-10 in the 3D Mel-RhS, as did the surrounding keratinocytes and fibroblasts. This cellular cross-talk-induced secretion of IL-10 in the Mel-RhS indicated the generation of an immune suppressive microenvironment. Culture supernatants from Mel-RhS interfered with monocyte-to-dendritic-cell differentiation, leading to the development of M2-like macrophages, which was in part prevented by antibody-mediated IL-10 blockade. Indeed, high-dimensional single-cell analysis revealed a shift within the monocyte population away from a CD163+PD-L1+ M2-like phenotype upon IL-10 blockade. Thus, the 3D configuration of the Mel-RhS model revealed a role for IL-10 in immune escape through misdirected myeloid differentiation, which would have been missed in classical monolayer cultures.
Wechselseitige Effekte von Gruppenkohäsion und Symptomen
Authors: Dinger Ulrike , Zilcha-Mano Sigal , Schauenburg Henning
Published: June 2020

Kohäsion ist ein bedeutsamer Teil gruppentherapeutischer Beziehungen und stellt einen potenziell kurativen Faktor dar, der nachfolgende Symptomverbesserungen erklären kann. Trotz der häufig belegten Korrelation zwischen erlebter Kohäsion und der Symptomschwere fehlen longitudinale Studien, in denen sowohl die zeitliche Abfolge von Kohäsion und Symptomveränderungen angemessen berücksichtigt und zusätzlich zwischen dem mittleren Level der Kohäsion einzelner Gruppenteilnehmer („between-person effect“) und der individuellen Veränderung („within-person effect“) differenziert wird. Diese Studie untersucht das Kohäsionserleben zur Patientengruppe auf einer Psychotherapiestation mit integrierter Tagesklinik. Vierzig depressive Patienten wurden im Rahmen einer randomisierten kontrollierten Studie zum Vergleich tagesklinischer und stationärer Psychotherapie rekrutiert. Alle Patienten gaben wöchentlich Auskunft über die Therapiebeziehungen (einschließlich Kohäsion) und die aktuelle Symptombelastung; für die Auswertung der Multilevel Daten wurde ein autoregressives cross-lagged Modell verwendet. Die Ergebnisse deuten auf eine wechselseitige Beeinflussung hin. Ein individueller Anstieg der Kohäsion war ein signifikanter Prädiktor für verbesserte Symptome, auch wenn für die vorherige Symptombelastung kontrolliert wurde. Umgekehrt war auch eine Symptomverbesserung prädiktiv für ein höheres Kohäsionserleben im Verlauf. Damit zeigt die Studie die Bedeutung der Beziehungsqualität zur Gruppe der Mitpatienten und weist auf eine wechselseitige Beeinflussung von Kohäsion und Symptomen hin. Allerdings müssen die Ergebnisse aufgrund der kleinen Stichprobe mit Vorsicht interpretiert werden.
Validation of thoracic aortic dimensions on ECG-triggered SSFP as alternative to contrast-enhanced MRA
Authors: Snel G. J. H. , Hernandez L. M. , Slart R. H. J. A. , Nguyen C. T. , Sosnovik D. E. , van Deursen V. M. , Dierckx R. A. J. O. , Velthuis B. K. , Borra R. J. H. , Prakken N. H. J.
Published: June 2020

Objectives

Assessment of thoracic aortic dimensions with non-ECG-triggered contrast-enhanced magnetic resonance angiography (CE-MRA) is accompanied with motion artefacts and requires gadolinium. To avoid both motion artefacts and gadolinium administration, we evaluated the similarity and reproducibility of dimensions measured on ECG-triggered, balanced steady-state free precession (SSFP) MRA as alternative to CE-MRA.

Methods

All patients, with varying medical conditions, referred for thoracic aortic examination between September 2016 and March 2018, who underwent non-ECG-triggered CE-MRA and SSFP-MRA (1.5 T) were retrospectively included (n= 30). Aortic dimensions were measured after double-oblique multiplanar reconstruction by two observers at nine landmarks predefined by literature guidelines. Image quality was scored at the sinus of Valsalva, mid-ascending aorta and mid-descending aorta by semi-automatically assessing the vessel sharpness.

Results

Aortic dimensions showed high agreement between non-ECG-triggered CE-MRA and SSFP-MRA (r= 0.99,p< 0.05) without overestimation or underestimation of aortic dimensions in SSFP-MRA (mean difference, 0.1 mm; limits of agreement, − 1.9 mm and 1.9 mm). Intra- and inter-observer variabilities were significantly smaller with SSFP-MRA for the sinus of Valsalva and sinotubular junction. Image quality of the sinus of Valsalva was significantly better with SSFP-MRA, as fewer images were of impaired quality (3/30) than in CE-MRA (21/30). Reproducibility of dimensions was significantly better in images scored as good quality compared to impaired quality in both sequences.

Conclusions

Thoracic aortic dimensions measured on SSFP-MRA and non-ECG-triggered CE-MRA were similar. As expected, SSFP-MRA showed better reproducibility close to the aortic root because of lesser motion artefacts, making it a feasible non-contrast imaging alternative.

Key Points

•SSFP-MRA provides similar dimensions as non-ECG-triggered CE-MRA.

•Intra- and inter-observer reproducibilities improve for the sinus of Valsalva and sinotubular junction with SSFP-MRA.

•ECG-triggered SSFP-MRA shows better image quality for landmarks close to the aortic root in the absence of cardiac motion.
Hemangioblastoma and von Hippel-Lindau disease: genetic background, spectrum of disease, and neurosurgical treatment
Authors: Klingler Jan-Helge , Gläsker Sven , Bausch Birke , Urbach Horst , Krauss Tobias , Jilg Cordula A. , Steiert Christine , Puzik Alexander , Neumann-Haefelin Elke , Kotsis Fruzsina , Agostini Hansjürgen , Neumann Hartmut P.H. , Beck Jürgen
Published: June 2020

Introduction

Hemangioblastomas are rare, histologically benign, highly vascularized tumors of the brain, the spinal cord, and the retina, occurring sporadically or associated with the autosomal dominant inherited von Hippel-Lindau (VHL) disease. Children or adults with VHL disease have one of > 300 known germline mutations of the VHL gene located on chromosome 3. They are prone to develop hemangioblastomas, extremely rarely starting at age 6, rarely at age 12–18, and, typically and almost all, as adults. There is a plethora of VHL-associated tumors and cysts, mainly in the kidney, pancreas, adrenals, reproductive organs, and central nervous system. Due to a lack of causal treatment, alleviation of symptoms and prevention of permanent neurological deficits as well as malignant transformation are the main task. Paucity of data and the nonlinear course of tumor progression make management of pediatric VHL patients with hemangioblastomas challenging.

Methods

The Freiburg surveillance protocol was developed by combining data from the literature and our experience of examinations of > 300 VHL patients per year at our university VHL center.

Results

Key recommendations are to start screening of patients at risk by funduscopy with dilated pupils for retinal tumors with admission to school and with MRI of the brain and spinal cord at age 14, then continue biannually until age 18, with emergency MRI in case of neurological symptoms. Indication for surgery remains personalized and should be approved by an experienced VHL board, but we regard neurological symptoms, rapid tumor growth, or critically large tumor/cyst sizes as the key indications to remove hemangioblastomas. Since repeated surgery on hemangioblastomas in VHL patients is not rare, modern neurosurgical techniques should encompass microsurgery, neuronavigation, intraoperative neuromonitoring, fluorescein dye-based intraoperative angiography, intraoperative ultrasound, and minimally invasive approaches, preceded in selected cases by endovascular embolization. Highly specialized neurosurgeons are able to achieve a very low risk of permanent morbidity for the removal of hemangioblastomas from the cerebellum and spinal cord. Small retinal tumors of the peripheral retina can be treated by laser coagulation, larger tumors by cryocoagulation or brachytherapy.

Conclusion

We consider management at experienced VHL centers mandatory and careful surveillance and monitoring of asymptomatic lesions are required to prevent unnecessary operations and minimize morbidity.
Tetraspanins in the regulation of mast cell function
Authors: Orinska Zane , Hagemann Philipp M. , Halova Ivana , Draber Petr
Published: June 2020

Mast cells (MCs) are long-living immune cells highly specialized in the storage and release of different biologically active compounds and are involved in the regulation of innate and adaptive immunity. MC degranulation and replacement of MC granules are accompanied by active membrane remodelling. Tetraspanins represent an evolutionary conserved family of transmembrane proteins. By interacting with lipids and other membrane and intracellular proteins, they are involved in organisation of membrane protein complexes and act as “molecular facilitators” connecting extracellular and cytoplasmic signaling elements. MCs express different tetraspanins and MC degranulation is accompanied by changes in membrane organisation. Therefore, tetraspanins are very likely involved in the regulation of MC exocytosis and membrane reorganisation after degranulation. Antiviral response and production of exosomes are further aspects of MC function characterized by dynamic changes of membrane organization. In this review, we pay a particular attention to tetraspanin gene expression in different human and murine MC populations, discuss tetraspanin involvement in regulation of key MC signaling complexes, and analyze the potential contribution of tetraspanins to MC antiviral response and exosome production. In-depth knowledge of tetraspanin-mediated molecular mechanisms involved in different aspects of the regulation of MC response will be beneficial for patients with allergies, characterized by overwhelming MC reactions.
Emergence delirium is associated with increased postoperative delirium in elderly: a prospective observational study
Authors: Zhang Yan , He Shu-Ting , Nie Bin , Li Xue-Ying , Wang Dong-Xin
Published: June 2020

Background

The clinical significance of emergence delirium remains unclear. The purpose of this study was to investigate the association between emergence delirium and postoperative delirium in elderly after general anesthesia and surgery.

Methods

This prospective observational study was done in a tertiary hospital in Beijing, China. Elderly patients (65–90 years) who underwent major noncardiac surgery under general anesthesia and admitted to the postanesthesia care unit (PACU) after surgery were enrolled. Emergence delirium was assessed with the Confusion Assessment Method for the Intensive Care Unit during PACU stay. Postoperative delirium was assessed with the Confusion Assessment Method during the first 5 postoperative days. The association between emergence delirium and postoperative delirium was analyzed with a multivariable logistic regression model.

Results

A total of 942 patients were enrolled and 915 completed the study. Emergence delirium developed in 37.0% (339/915) of patients during PACU stay; and postoperative delirium developed in 11.4% (104/915) of patients within the first 5 postoperative days. After adjusted confounding factors, the occurrence of emergence delirium is independently associated with an increased risk of postoperative delirium (OR 1.717, 95% CI 1.078–2.735,P = 0.023). Patients with emergence delirium stayed longer in PACU and hospital after surgery, and developed more non-delirium complications within 30 days.

Conclusions

Emergence delirium in elderly admitted to the PACU after general anesthesia and major surgery is independently associated with an increased risk of postoperative delirium. Patients with emergence delirium had worse perioperative outcomes.

Chinese Clinical Trial Registry (chictr.org.cn)ChiCTR-OOC-17012734
Voltammetry coupled with impedance spectroscopy
Authors: Pajkossy Tamás
Published: June 2020

Dynamic EIS (dEIS) is the joint use of cyclic voltammetry and electrochemical impedance spectroscopy. A method is planned for data evaluation which involves transformations yielding potential program invariant forms of certain characteristic functions. This way of calculation is illustrated by the analysis of two archetypes of electrochemical kinetics. A future task is to develop the related theories and to perform demonstration experiments aimed at establishing dEIS as a robust, general-purpose technique for characterizing electrochemical systems.
Tidal response to sea level rise and bathymetric changes in the German Wadden Sea
Authors: Wachler Benno , Seiffert Rita , Rasquin Caroline , Kösters Frank
Published: June 2020

Tidally dominated coasts are directly affected not only by projected rise in mean sea level, but also by changes in tidal dynamics due to sea level rise and bathymetric changes. By use of a hydrodynamic model, which covers the entire German Bight (South-Eastern North Sea), we analyse the effects of sea level rise and potential bathymetric changes in the Wadden Sea on tidal current velocities. The model results indicate that tidal current velocities in the tidal inlets and channels of the Wadden Sea are increased in response to sea level rise. This is explained by the increased ratio of tidal prism to tidal inlet cross-sectional area, which is due to the characteristic hypsometry of tidal basins in the Wadden Sea including wide and shallow tidal flats and relatively narrow tidal channels. The results further indicate that sea level rise decreases ebb dominance and increases flood dominance in tidal channels. This is, amongst others, related to a decreased intertidal area again demonstrating the strong interaction between tidal wave and tidal basin hypsometry in the Wadden Sea. The bathymetry scenario defined in this study includes elevated tidal flats and deepened tidal channels, which is considered a potential future situation under accelerated sea level rise. Application of these bathymetric changes to the model mostly compensates the effects of sea level rise. Furthermore, changes in current velocity due to the altered bathymetry are in the same order of magnitude as changes due to mean sea level rise. This highlights the significance of considering potential bathymetric changes in the Wadden Sea for regional projections of the tidal response to sea level rise.
Decades of Tight Fiscal Policy Have Left the Health Care System in Italy Ill-Prepared to Fight the COVID-19 Outbreak
Authors: Prante Franz J. , Bramucci Alessandro , Truger Achim
Published: June 2020

Although austerity was particularly strong in the aftermath of the economic crisis of 2008 and its consequences in the euro area, Italian fiscal policies have been characterised by tough consolidation periods ever since the 1990s.
On the Macroeconomic and Social Impact of the Coronavirus Pandemic in Latin America and the Developing World
Authors: Proaño Christian R.
Published: June 2020

While the COVID-19 pandemic posits a significant challenge to all societies around the world, it also reveals in the most dramatic manner the many abysmal differences between so-called advanced economies and the developing world.
How the COVID-19 Pandemic Is Reshaping the Trade Landscape and What to Do About It
Authors: Jean Sébastien
Published: June 2020

The COVID-19 pandemic carries heavy threats, and preserving stable and coordinated international trade relations will be essential to avoid catastrophic disorders or conflicts.
Why Current EU Proposals for Corona-Related Financial Aid Cannot Replace Coronabonds
Authors: Dullien Sebastian , Theobald Thomas , Tober Silke , Watt Andrew
Published: June 2020

With public debt-to-GDP levels now set to surpass post-war records and Italy’s ratio approaching levels reached in Greece on the eve of the country’s debt restructuring in early 2012, fears of a return of the sovereign debt crisis have emerged.
A European Mechanism for the Issuance and Initial Distribution of Debt Securities
Authors: Pavlidis Georgios
Published: June 2020

Although the European Union (EU) has implemented initiatives and common rules regarding securities settlements, no similar integration initiatives have been proposed for the issuance and initial distribution of debt securities. The EU does not function as a single market given that issuers of euro debt instruments still have to use multiple and non-harmonised channels and procedures. A harmonised European framework for the issuance and initial distribution of debt securities or the establishment of a new European market infrastructure service is widely considered a way to create a deep and liquid single market for debt instruments. While such a paradigm shift promises significant improvements compared with the existing debt issuance and distribution landscape, a hasty and poorly designed public intervention would risk distorting the market, thereby increasing complexity and bringing more fragmentation.
Cytochrome P450-mediated N-demethylation of noscapine by whole-cell biotransformation: process limitations and strategies for optimisation
Authors: Richards Luke , Jarrold Ailsa , Bowser Tim , Stevens Geoffrey W , Gras Sally L
Published: June 2020

Cytochrome P450 enzymes catalyse reactions of significant industrial interest but are underutilised in large-scale bioprocesses due to enzyme stability, cofactor requirements and the poor aqueous solubility and microbial toxicity of typical substrates and products. In this work, we investigate the potential for preparative-scale N-demethylation of the opium poppy alkaloid noscapine by a P450BM3 (CYP102A1) mutant enzyme in a whole-cell biotransformation system. We identify and address several common limitations of whole-cell P450 biotransformations using this model N-demethylation process. Mass transfer into Escherichia coli cells was found to be a major limitation of biotransformation rate and an alternative Gram-positive expression host Bacillus megaterium provided a 25-fold improvement in specific initial rate. Two methods were investigated to address poor substrate solubility. First, a biphasic biotransformation system was developed by systematic selection of potentially biocompatible solvents and in silico solubility modelling using Hansen solubility parameters. The best-performing biphasic system gave a 2.3-fold improvement in final product titre compared to a single-phase system but had slower initial rates of biotransformation due to low substrate concentration in the aqueous phase. The second strategy aimed to improve aqueous substrate solubility using cyclodextrin and hydrophilic polymers. This approach provided a fivefold improvement in initial biotransformation rate and allowed a sixfold increase in final product concentration. Enzyme stability and cell viability were identified as the next parameters requiring optimisation to improve productivity. The approaches used are also applicable to the development of other pharmaceutical P450-mediated biotransformations.
Climatic factors controlling stem growth of alien tree species at a mesic forest site: a multispecies approach
Authors: Hoffmann Nils , Heinrichs Steffi , Schall Peter , Vor Torsten
Published: June 2020

The introduction of non-native species with various ecological and functional traits to European forests may be a potential tool for mitigating climate risks. We analyzed the growth sensitivity to climate of seven alien (Acer rubrum,Betula maximowicziana,Castanea sativa,Cryptomeria japonica,Metasequoia glyptostroboides,Thuja plicataandTsuga heterophylla) and two native (Fagus sylvaticaandPicea abies) tree species on a productive forest site in western Germany in order to assess their potential suitability in light of climate change. Retrospective basal area increment at breast height (BAI) and total stem volume increment (VI) were statistically related to a total of 11 multiscale climatic variables showing minor discrepancies between BAI and VI in climatic sensitivity. Across the tree species, the strongest climate signals were found for the standardized precipitation evapotranspiration index (spei), vapor pressure deficit (vpd) and the number of frost days (nfr) representing water availability, heat and coldness, respectively. Growth of most species was positively affected by mild winters and growing season spei. Importance of the investigated variables differed among tree species with, e.g.,C. sativaandT. plicatabeing mainly driven by winter vpd andA. rubrum,C. japonicaandP. abiesby water availability in the growing seasons. We conclude that particularly more anisohydric species (e.g.,C. sativa) may profit from their low sensitivity to drier conditions. Highly sensitive and isohydric species (e.g.,A. rubrum)will undergo significant growth reductions when climate becomes more variable.
Biological Energy and the Experiencing Subject
Authors: Gamper Johan
Published: June 2020

As physical things have mathematical properties we in this paper let mental things have biological properties. The work is based on recent metaphysical findings that shows that there could be interfaces between separate ontological domains. According to this view there could be mathematical objects, physical objects, and also mental objects. The aim of this study is to establish a view of the biological object that allows it to possibly generate the experiencing subject. Based on the notion that energy per se is related to the ability of a system to do some work, biological energy is defined as a biological object’s ability to recover from the load it is exposed to. Introducing the concept of the experiencing subject, the experiencing subject would be the agent experiencing the biological object’s need of recovery from the load it is exposed to. Once established, the experiencing subject may develop non-biological needs. On this basis experiencing subjects have biological properties without being biological in exactly the same manner as physical things have mathematical properties without being mathematical (would that be the case).
Expression and function of epithelial cell adhesion molecule EpCAM: where are we after 40 years?
Authors: Gires Olivier , Pan Min , Schinke Henrik , Canis Martin , Baeuerle Patrick A.
Published: June 2020

EpCAM (epithelial cell adhesion molecule) was discovered four decades ago as a tumor antigen on colorectal carcinomas. Owing to its frequent and high expression on carcinomas and their metastases, EpCAM serves as a prognostic marker, a therapeutic target, and an anchor molecule on circulating and disseminated tumor cells (CTCs/DTCs), which are considered the major source for metastatic cancer cells. Today, EpCAM is reckoned as a multi-functional transmembrane protein involved in the regulation of cell adhesion, proliferation, migration, stemness, and epithelial-to-mesenchymal transition (EMT) of carcinoma cells. To fulfill these functions, EpCAM is instrumental in intra- and intercellular signaling as a full-length molecule and following regulated intramembrane proteolysis, generating functionally active extra- and intracellular fragments. Intact EpCAM and its proteolytic fragments interact with claudins, CD44, E-cadherin, epidermal growth factor receptor (EGFR), and intracellular signaling components of the WNT and Ras/Raf pathways, respectively. This plethora of functions contributes to shaping intratumor heterogeneity and partial EMT, which are major determinants of the clinical outcome of carcinoma patients. EpCAM represents a marker for the epithelial status of primary and systemic tumor cells and emerges as a measure for the metastatic capacity of CTCs. Consequentially, EpCAM has reclaimed potential as a prognostic marker and target on primary and systemic tumor cells.
Rereading Durkheim in light of Jewish law: how a traditional rabbinic thought-model shapes his scholarship
Authors: Winfield Taylor Paige
Published: June 2020

When studying the work of Émile Durkheim, scholars must consider how his intellectual development in a traditional Jewish environment contributed to and informed his ideas. This article details how Durkheim’s upbringing endowed him with a traditional rabbinic thought-model. The author analyzes five of Durkheim’s major works to argue that the system of classification, language, and style of argument Durkheim used to define concepts in his scholarship mirror streams of rabbinic thought. The article builds off the sociology of knowledge to illuminate how Durkheim employed his codified knowledge of biblical texts and modern Jews to bolster his arguments, and reveals the subtler ways he demonstrates his tacit knowledge of the texts and argument styles. The article ends with an exploration of how conceptual frameworks from the sociology of knowledge may be applied to other leading sociological thinkers—how the modes of thinking instilled during formative years may orient scholarship and the benefits and limitations of this approach.
Trust in the investor relationship marketing of startups: a systematic literature review and research agenda
Authors: Kaiser Manuel , Berger Elisabeth S. C.
Published: June 2020

An important task of entrepreneurs is the management of investor relations. Past literature has emphasized the role of trust for managing relationships and regulating their quality. However, the landscape of investors has changed due to digitalization, so that new players have joined and expanded the investor offer. Entrepreneurs also often enter into relationships with multiple investors, which can challenge investor relationship marketing. To provide an overview, we conduct a structured literature review on the entrepreneur’s relationship marketing with four key investors: venture capitalists (VCs), business angels (BAs), banks, and crowd funders. The paper improves the understanding of trust as a concept in the management of investor relations and identifies directions for future research. The results show that research has predominantly studied trust in the VC–entrepreneur relationship. Across different investors, the primary focus has been on factors that influence trust building, especially investor communication and entrepreneur–investor fit. Furthermore, the results show that trust has an influence on cooperation by strengthening the relationship and reducing risk.
Efficacy of the FDA nozzle benchmark and the lattice Boltzmann method for the analysis of biomedical flows in transitional regime
Authors: Jain Kartik
Published: June 2020

Flows through medical devices as well as in anatomical vessels despite being at moderate Reynolds number may exhibit transitional or even turbulent character. In order to validate numerical methods and codes used for biomedical flow computations, the US Food and Drug Administration (FDA) established an experimental benchmark, which was a pipe with gradual contraction and sudden expansion representing a nozzle. The experimental results for various Reynolds numbers ranging from 500 to 6500 were publicly released. Previous and recent computational investigations of flow in the FDA nozzle found limitations in various CFD approaches and some even questioned the adequacy of the benchmark itself. This communication reports the results of a lattice Boltzmann method (LBM) – based direct numerical simulation (DNS) approach applied to the FDA nozzle benchmark for transitional cases of Reynolds numbers 2000 and 3500. The goal is to evaluate if a simpleoff the shelfLBM would predict the experimental results without the use of complex models or synthetic turbulence at the inflow. LBM computations with various spatial and temporal resolutions are performed—in the extremities of 45 million to 2.88 billion lattice cells—executed respectively on 32 CPU cores of a desktop to more than 300,000 cores of a modern supercomputer to explore and characterize miniscule flow details and quantify Kolmogorov scales. The LBM simulations transition to turbulence at a Reynolds number 2000 like the FDA’s experiments and acceptable agreement injet breakdown locations, average velocity, shear stress, andpressureis found for both the Reynolds numbers.
Reinforcement learning for an intelligent and autonomous production control of complex job-shops under time constraints
Authors: Altenmüller Thomas , Stüker Tillmann , Waschneck Bernd , Kuhnle Andreas , Lanza Gisela
Published: June 2020

Reinforcement learning (RL) offers promising opportunities to handle the ever-increasing complexity in managing modern production systems. We apply a Q-learning algorithm in combination with a process-based discrete-event simulation in order to train a self-learning, intelligent, and autonomous agent for the decision problem of order dispatching in a complex job shop with strict time constraints. For the first time, we combine RL in production control with strict time constraints. The simulation represents the characteristics of complex job shops typically found in semiconductor manufacturing. A real-world use case from a wafer fab is addressed with a developed and implemented framework. The performance of an RL approach and benchmark heuristics are compared. It is shown that RL can be successfully applied to manage order dispatching in a complex environment including time constraints. An RL-agent with a gain function rewarding the selection of the least critical order with respect to time-constraints beats heuristic rules strictly by picking the most critical lot first. Hence, this work demonstrates that a self-learning agent can successfully manage time constraints with the agent performing better than the traditional benchmark, a time-constraint heuristic combining due date deviations and a classical first-in-first-out approach.
Modelling of selected hydrodynamic and hydrochemical parameters of a geothermal water system: an example of Cieplice therapeutic waters
Authors: Liber-Makowska Elżbieta , Kiełczawa Barbara
Published: June 2020

Article presents results of long-period observations made in the most interesting and perspective geothermal area of Poland. Moreover, Cieplice is one of the oldest spa resort in Poland where thermal waters are used for treating purposes for centuries. That is the only one region in Poland with geothermal waters in granitic rocks and this can be interesting for international readers. The region of Jelenia Góra-Cieplice has been considered a prospective area of geothermal water occurrence for many years. The earliest evidence of balneological use of these waters dates from the thirteenth century. Currently, they are being used for therapeutic purposes, and since 2014 also for recreation. The character of changes in intake discharge, water temperature and wellhead pressure observed in 1956–2019, as well as calculations of specific values (the mean, the minimum, the maximum and the standard deviation) have demonstrated considerable diversity and significant variation in these operating parameters. The main cause of changes in these parameters is changing intake operation conditions. Currently, thermal waters are being extracted chiefly from the deepened borehole C-1. Increased extraction from this intake has resulted in decreases in the temperature of thermal water from springs and borehole C-2 and a decline in their discharge or even the disappearance of their outflow. The exploitation of borehole C-1 in such conditions has also caused a drop in water pressure at its head (from 0.49 to 0.34 MPa) accompanied by an increase in water temperature (from 58 to 82 °C). The increase in water temperature is indicative of the presence of deep circulation waters in this intake. Based on the results of long-term (1963–2018) physico-chemical analyses of waters from particular intakes and deep boreholes, dominant chemical types have been distinguished: Na-HCO3–SO4 and Na–SO4–HCO3, containing fluorides and silica. By using chemical geothermometers, deposit temperatures of Cieplice thermal waters have been estimated (111–138 °C). The obtained results were verified by analysing the degree of saturation of these waters with selected rock-forming minerals by means of GeoT application. The deposit temperature estimated by modelling is c. 123 °C.
An assessment of the contribution of air pollution to the weathering of limestone heritage in Malta
Authors: Grøntoft Terje , Cassar JoAnn
Published: June 2020

Malta is known for its limestone megalithic temples of which many are inscribed on the UNESCO World Heritage List. A variation of this limestone was historically, and until very few years ago, a primary building material in Malta. The temples are subject to various environmental influences which until recently have led to several collapses due in part to serious stone surface and infill loss. As a protection measure, open-sided shelters have been built over three of these temples. This work assesses the degrading influence of air pollution (nitrogen dioxide, ozone, particle matter, sulfur dioxide, and acidity in rain) on the temples, in combination and comparison with the influence of other environmental factors (relative humidity, temperature, precipitation, moisture, sea salt, wind) and in this respect evaluates the potential protective effect of the shelters. The variation in air pollution weathering of limestone exposed outdoor in Malta was calculated by exposure–response functions from the ICP-materials programme and compared with measured values, and its contribution to the deterioration of the temples was evaluated. The difference between urban and rural locations in Malta, in the first year of atmospheric chemical weathering of limestone due to air pollution, was found to be about one micrometer loss of stone surface. This is probably less than the annual variations due to the influence of natural climatic factors, and small compared to the present annual variations in continental Europe. The deposition of sea salt and presence of salts on and in the limestone megaliths and changes in salt-crystallization events due to relative humidity fluctuations, inside and outside the shelters, will account for more of the variations in the first year of weathering of Globigerina limestone than variations in air pollution. The deterioration will also be related to temperature (including condensation events), wind parameters and rainfall, as well as ground water replenished from areas beyond the shelter.
Utility of angiography–physiology coregistration maps during percutaneous coronary intervention in clinical practice
Authors: Matsuo Akiko , Kasahara Takeru , Ariyoshi Makoto , Irie Daisuke , Isodono Koji , Tsubakimoto Yoshinori , Sakatani Tomohiko , Inoue Keiji , Fujita Hiroshi
Published: June 2020

This study aimed to evaluate the utility and feasibility of physiological maps coregistered with angiograms using the pullback of a pressure guidewire with continuous instantaneous wave-free ratio (iFR) measurements. iFR pullback was obtained for 70 lesions from 70 patients with stable angina pectoris using SyncVision (Philips Corp.). Physiological maps were created, whereby the post-intervention iFR (post-iFR) was predicted as iFRpred. The iFR gap was defined if the difference between the iFRpred and post-iFR was ≥ 0.3. The lesion morphology changed from that during the physiological assessment to that during the angiographic assessment in 26 lesions (37.1%). In particular, 22.6% of angiographic tandem lesions changed to physiological focal lesions. The mean pre-intervention iFR, post-iFR, and iFRpred were 0.73 ± 0.17, 0.90 ± 0.06, and 0.93 ± 0.05, respectively. The mean difference between the iFRpred and post-iFR was 0.029 ± 0.099, with 95% limits of agreement of -0.070–0.128. iFR gaps occurred in 28 patients (40%). Notably, a new iFR gradient causing a ≥ 0.03 iFR drop after stenting occurred in 11 (15.7%) cases. The study patients were divided into two groups according to biases between post-iFR and iFRpred < 0.03 (good concordance group) or ≥ 0.03 (poor concordance group). The pre-intervention heart rate was the only independent predictor of poor concordance (odds ratio, 0.936; 95% confidence interval 0.883–0.992; p = 0.027). Physiological maps under resting conditions may contribute to a reduction in unnecessary stent placements without missing lesions requiring treatment. However, the predictive accuracy of post-iFR performance in the present study was slightly lower than that in the previous reports.