bluuebunny/crossref_metadata_2025 huggingface dataset:
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

The 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

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

In 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

In 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.
On the Means of Jordan’s Totient Function
Authors: Esfandiari Mohammadreza
Published: February 2020

In this paper, we study some important means of Jordan’s totient function, especially, we obtain asymptotic formula for geometric mean and harmonic mean. We also study alternating sums of Jordan’s totient function and Carleman’s inequality for this function.
Usability Assessment of Steering Wheel Control Interfaces in Motorsport
Authors: Brown James W. H. , Stanton Neville A. , Revell Kirsten M. A.
Published: February 2020

In order to assess the usability of steering wheel control interfaces in motorsport, it is necessary to employ a set of appropriate methods. The method selection process first involves identifying the relevant motorsport-based usability criteria. The unique factors associated with context of use in motorsport are then defined. These are employed to synthesize a set of key performance indicators (KPIs) that require specific analysis. The first KPI relates to error rates; these should be minimized, particularly under high cognitive load on the primary. The second KPI involves task times; these should be minimized not just to reduce distraction, but also to improve competitive performance. The third KPI states that usability should be optimized to minimize visual distraction. The fourth KPI advocates the minimizing of interface task load to reduce the effect on the primary task. The final KPI states that interface functionality should be easy to learn and recall. The KPIs provide clear goals to guide the identification of the most appropriate methods for each aspect of usability. Methods categories are devised and sets of appropriate methods selected based on the KPIs. These then combine into a toolset with an associated application process with the overall goal of providing a means by which motorsport interfaces may be both analysed and improved.
WHODrug: A Global, Validated and Updated Dictionary for Medicinal Information
Authors: Lagerlund Olof , Strese Sara , Fladvad Malin , Lindquist Marie
Published: February 2020

The WHODrug medicinal information dictionary is a worldwide source of global medicinal information with the aim to facilitate the coding of medications in clinical trials as well as identification of medication-related problems when monitoring patient safety, thereby supporting the development and usage of effective and safe medications. WHODrug contains individual trade names, active ingredients and additional information such as marketing authorisation holder, country of sale, pharmaceutical form and strength. All related medications are linked using a structured WHODrug alphanumeric code, connecting trade names and variation of the ingredient with the active moiety of the ingredient. Medications in WHODrug are classified using the ATC system and clustered into Standardised Drug Groupings, to allow for grouping of medications with one or more properties in common. The built-in data structure and the classification of medications in WHODrug facilitate various ways of aggregating medications for identification and analysis of possible adverse drug reactions. The different information levels in WHODrug are used to explore the relationship between a medication or a class of medications and an adverse event. By using WHODrug in clinical trials and post-marketing safety, accurate and standardised medication information can be achieved globally and allow easy information exchange. To meet the demands of WHODrug users from the pharmaceutical industry, academia and regulatory authorities, it is relevant to keep the dictionary comprehensive, validated and constantly updated on a global scale.
Furstenberg boundaries for pairs of groups
Authors: MONOD NICOLAS
Published: February 2020

Furstenberg has associated to every topological group $G$ a universal boundary $\unicode[STIX]{x2202}(G)$. If we consider in addition a subgroup $H<G$, the relative notion of $(G,H)$-boundaries admits again a maximal object $\unicode[STIX]{x2202}(G,H)$. In the case of discrete groups, an equivalent notion was introduced by Bearden and Kalantar (Topological boundaries of unitary representations. Preprint, 2019, arXiv:1901.10937v1) as a very special instance of their constructions. However, the analogous universality does not always hold, even for discrete groups. On the other hand, it does hold in the affine reformulation in terms of convex compact sets, which admits a universal simplex $\unicode[STIX]{x1D6E5}(G,H)$, namely the simplex of measures on $\unicode[STIX]{x2202}(G,H)$. We determine the boundary $\unicode[STIX]{x2202}(G,H)$ in a number of cases, highlighting properties that might appear unexpected.
Attractors associated to a family of hyperbolic -adic plane automorphisms
Authors: PETSCHE CLAYTON
Published: February 2020

We consider a certain two-parameter family of automorphisms of the affine plane over a complete, locally compact non-Archimedean field. Each of these automorphisms admits a chaotic attractor on which it is topologically conjugate to a full two-sided shift map, and the attractor supports a unit Borel measure which describes the distribution of the forward orbit of Haar-almost all points in the basin of attraction. We also compute the Hausdorff dimension of the attractor, which is non-integral.
Radial symmetry of minimizers to the weighted Dirichlet energy
Authors: Koski Aleksis , Onninen Jani
Published: February 2020

We consider the problem of minimizing the weighted Dirichlet energy between homeomorphisms of planar annuli. A known challenge lies in the case when the weightλdepends on the independent variablez. We prove that for an increasing radial weightλ(z) the infimal energy within the class of all Sobolev homeomorphisms is the same as in the class of radially symmetric maps. For a general radial weightλ(z) we establish the same result in the case when the target is conformally thin compared to the domain. Fixing the admissible homeomorphisms on the outer boundary we establish the radial symmetry for every such weight.
FROM TOPOLOGIES OF A SET TO SUBRINGS OF ITS POWER SET
Authors: JABALLAH ALI , JARBOUI NOÔMEN
Published: February 2020

Let $X$ be a nonempty set and ${\mathcal{P}}(X)$ the power set of $X$. The aim of this paper is to identify the unital subrings of ${\mathcal{P}}(X)$ and to compute its cardinality when it is finite. It is proved that any topology $\unicode[STIX]{x1D70F}$ on $X$ such that $\unicode[STIX]{x1D70F}=\unicode[STIX]{x1D70F}^{c}$, where $\unicode[STIX]{x1D70F}^{c}=\{U^{c}\mid U\in \unicode[STIX]{x1D70F}\}$, is a unital subring of ${\mathcal{P}}(X)$. It is also shown that $X$ is finite if and only if any unital subring of ${\mathcal{P}}(X)$ is a topology $\unicode[STIX]{x1D70F}$ on $X$ such that $\unicode[STIX]{x1D70F}=\unicode[STIX]{x1D70F}^{c}$ if and only if the set of unital subrings of ${\mathcal{P}}(X)$ is finite. As a consequence, if $X$ is finite with cardinality $n\geq 2$, then the number of unital subrings of ${\mathcal{P}}(X)$ is equal to the $n$th Bell number and the supremum of the lengths of chains of unital subalgebras of ${\mathcal{P}}(X)$ is equal to $n-1$.
POWER PARTITIONS AND SEMI--FIBONACCI PARTITIONS
Authors: ALANAZI ABDULAZIZ M. , MUNAGI AUGUSTINE O. , NYIRENDA DARLISON
Published: February 2020

Andrews [‘Binary and semi-Fibonacci partitions’, J. Ramanujan Soc. Math. Math. Sci.7(1) (2019), 1–6] recently proved a new identity between the cardinalities of the set of semi-Fibonacci partitions and the set of partitions into powers of 2 with all parts appearing an odd number of times. We extend the identity to the set of semi-$m$-Fibonacci partitions of $n$ and the set of partitions of $n$ into powers of $m$ in which all parts appear with multiplicity not divisible by $m$. We also give a new characterisation of semi-$m$-Fibonacci partitions and some congruences satisfied by the associated number sequence.
DISTINCT SOLUTIONS TO GENERATED JACOBIAN EQUATIONS CANNOT INTERSECT
Authors: RANKIN CALE
Published: February 2020

We prove that if two$C^{1,1}(\unicode[STIX]{x1D6FA})$solutions of the second boundary value problem for the generated Jacobian equation intersect in$\unicode[STIX]{x1D6FA}$then they are the same solution. In addition, we extend this result to$C^{2}(\overline{\unicode[STIX]{x1D6FA}})$solutions intersecting on the boundary, via an additional convexity condition on the target domain.
Cameroon's relations toward Nigeria: a foreign policy of pragmatism
Authors: Amin Julius A.
Published: February 2020

Existing literature argues that the tactics of Cameroon foreign policy have been conservative, weak and timid. This study refutes that perspective. Based on extensive and previously unused primary sources obtained from Cameroon's Ministry of External Relations and from the nation's archives in Buea and Yaoundé, this study argues that Cameroon's foreign policy was neither timid nor makeshift. Its strategy was one of pragmatism. By examining the nation's policy toward Nigeria in the reunification of Cameroon, the Nigerian civil war, the Bakassi Peninsula crisis and Boko Haram, the study maintains that, while the nation's policy was cautious, its leaders focused on the objectives and as a result scored major victories. The study concludes by suggesting that President Paul Biya invokes the same skills he used in foreign policy to address the ongoing Anglophone problem, a problem that threatens to unravel much of what the country has accomplished.
Government–donor relations in Sierra Leone: who is in the driving seat?
Authors: Harris David , Conteh Felix Marco
Published: February 2020

Since the cessation of conflict in 2002, Sierra Leone has experienced extraordinary levels of involvement from Western donors. Paradoxically, while relationships are often portrayed on the ground as strong with significant donor influence, our research shows considerable fluidity in individual and institutional relationships. The article disaggregates donor–government relations at various levels over a short but crucial period, 2010–16, asking in each case who occupies the driving seat. In so doing, the article interrogates the concept of ‘extraversion’, investigating to what extent government – and indeed donors – has space in which to manoeuvre and how and why government and donors act as they do in this space. The period 2010–16 is of particular interest due to extreme iron ore price volatility and the Ebola epidemic of 2014–15. The article adds much-needed critique and empirical evidence to the debate on donor influence and ‘extraversion’.
On overcoming the culture–nature divide: a panpsychist proposal
Authors: Leidenhag Joanna
Published: February 2020

Within the recently published volumes, Knowing Creation and Christ and the Created Order, several authors argue that the theological category of creation can help contemporary society overcome the modern, and ecologically harmful, bifurcation between nature and culture. This paper supplements this important argument by showing how theological panpsychism, an ontology inspired by current debates within analytic philosophy of mind, can help theologians articulate a metaphysically robust and trinitarian doctrine of creation.
Heterodox Hegels: heresiology in de Lubac and Bulgakov
Authors: Shaun Coyle Justin
Published: February 2020

This paper considers two twentieth-century heresiological critiques of G. W. F. Hegel. That Henri de Lubac and Sergius Bulgakov should both worry at Hegel's ‘heresy’ is hardly surprising. More surprising, however, is how and that each charges Hegel with a different heresy. Though de Lubac's heresiological critique has proven more influential, I commend Bulgakov's. The paper concludes by querying the very strategy of assaying philosophers like Hegel heresiologically.
International refugee protection and the primary institutions of international society
Authors: Nantermoz Olivia
Published: February 2020

Refugees are often considered as a source of disorder if not fundamental threat to international society. In contrast, and drawing from an English School approach, this article argues that the figure of the refugee is foundational to the constitution of both modern international society and its agent, the sovereign territorial state; hence refugee protection represents a primary institution of international society. Starting with conceptual and methodological considerations for studying primary institutions, the article then highlights the longstanding and widespread state practice of granting asylum. It is shown that on the one hand, the figure of the refugee serves to consolidate and naturalise the nation/state/territory trinity underpinning the modern state system; and on the other hand, protecting refugees plays a central role in the construction of statist self-identities as liberal, humanitarian, and altruistic agents. The last section of the article turns to the politics of contestation of refugee protection, examining domestic, regional, and international reactions to ‘anti-refugee’ policies in the United States, Hungary, and Australia. The considerable amount of criticism generated by these restrictive policies, it is argued, evidence the enduring importance and relevance of refugee protection in (and for) international society.
RELATION AS KEY TO GOD'S KNOWLEDGE OF PARTICULARS IN THE TAHĀFUT AL-TAHĀFUT AND THE ḌAMĪMA: A CROSS-TALK BETWEEN AVERROES, AL-ĠAZĀLĪ AND AVICENNA
Authors: Brenet Jean-Baptiste
Published: February 2020

This article deals with the divine knowledge of particulars in Averroes’ Tahāfut al-tahāfut and Ḍamīma. It examines how the concept of relation, generally neglected, is at the heart of the dispute between Avicenna, al-Ġazālī, and the Commentator. In al-Ġazālī’s eyes, Avicenna's misconception of divine knowledge “in a universal way” is based on a misuse of relation in the case of God's knowledge. If particulars change and God does not, his knowledge of particulars, insofar as it undergoes change, can be considered a pure relation without ontological consequences. Averroes contests both al-Ġazālī’s criticism and his proposal, despite the fact that, for different reasons involving the coming-to-be of human knowledge, he too employs the notion of pure relation in his Long Commentary on the Physics.
Percolation on an infinitely generated group
Authors: Georgakopoulos Agelos , Haslegrave John
Published: February 2020

We give an example of a long range Bernoulli percolation process on a group non-quasi-isometric with ℤ, in which clusters are almost surely finite for all values of the parameter. This random graph admits diverse equivalent definitions, and we study their ramifications. We also study its expected size and point out certain phase transitions.
The new town of Angra (Terceira, the Azores): confirming a contested urban planning history using reverse historical analysis and flood modelling tools
Authors: Leite Antonieta , Leitão João
Published: February 2020

The Portuguese discovered the uninhabited Azores archipelago in 1427 and started to settle it during the fifteenth century. Angra, located on Terceira Island, soon became the most important Azorean city, leading to rapid urban development. This article investigates the overlooked role of streams in the rise of Angra as a pivotal Atlantic urban centre. Through the intersection of historical and flood modelling methods, it makes a unique contribution to our understanding of Angra's urban morphologic development, highlighting the potential of applying urban flood modelling to analysis of the rise of coastal urban settlement.
Ontogeny of the digestive tract of Brycon amazonicus (Teleostei, Bryconidae) under culture conditions: from hatching to juvenile stage
Authors: Neumann Erika , Paes Maria do Carmo Faria , Mendes José Mário Ribeiro , Braga Francisco Manoel de Souza , Nakaghi Laura Satiko Okada
Published: February 2020

In the present study, the morphological development of the Brycon amazonicus digestive tract is described to provide basic knowledge for nutritional studies and, therefore, increase the survival of this species during larviculture. Samples were collected from hatching up to 25 days of age, measured, processed and observed under a stereomicroscope and light microscopy. Newly hatched larvae presented their digestive tract as a straight tube, dorsal to the yolk sac, lined with a single layer of undifferentiated cells. At 24 h post-hatching (hPH), the buccopharyngeal cavity was open, but the posterior region of the digestive tube remained closed. At 25 hPH, the digestive tube was completely open and could be divided into buccopharyngeal cavity, oesophagus and intestine. At 35 hPH, the intestine presented a dilatation in the proximal region, which had the function of storing food. Differentiation of the stomach started at 83 hPH, and mucous cells were observed in the epithelium. These cells are important in the production of mucus, whose function is to protect the organ against acidity, although the gastric glands began developing only from 171 hPH, when three stomach regions were observed: cardiac, fundic and pyloric. The gastric glands were observed in the cardiac region, indicating that this organ already had digestive functionality. From 243 hPH, the absorption and assimilation of nutrients were already possible but, only from 412 hPH, the digestive tract was completely developed and functional.
Effects of a kindergarten intervention on vegetables served and staff’s food-related practices: results of a cluster randomised controlled trial – the BRA study
Authors: Himberg-Sundet Anne , Kristiansen Anne Lene , Frost Andersen Lene , Bjelland Mona , Lien Nanna
Published: February 2020

Objective:

The aim of the current study was to evaluate the effect on frequency, variety and amount of vegetables served and staff’s food-related practices in the multicomponent BRA intervention.

Design:

Cluster randomised controlled trial, conducted between Spring 2015 and Spring 2016. For allocation of the kindergartens, a stratified block randomisation was used. Data were collected in three ways: (i) a questionnaire for pedagogical leaders assessing the variety and frequency of vegetables served, including staff’s food-related practices assumed to be related to vegetable intake; (ii) a questionnaire for kindergarten assistants assessing staff’s food-related practices; (iii) a 5-d weighted vegetable diary assessing amount of vegetables served in a department.

Setting:

The target group for this study was public and private kindergartens in the counties of Vestfold and Buskerud, Norway.

Participants:

A total of seventy-three kindergartens participated.

Results:

At follow-up I, the amount of vegetables served increased by approximately 20 g per person per day (P = 0·002), and the variety in served vegetables increased by one-and-a-half kind per month (P = 0·014) in the intervention group compared to the control group. No effects on the frequency of vegetables served or on staff’s food-related practices were found.

Conclusions:

The BRA intervention was successful in increasing the amount and variety of vegetables served within intervention kindergartens. Further research is needed to understand the mechanisms that can affect the staff’s food-related practices.
Contour bunding technology-evidence and experience in the semiarid region of southern Mali
Authors: Birhanu Birhanu Zemadim , Traoré Kalifa , Sanogo Karamoko , Tabo Ramadjita , Fischer Gundula , Whitbread Anthony Michael
Published: February 2020

Land and water management practices have been widely implemented in rural Mali since the 1980s to improve agricultural productivity and erosion control. Under conditions of recurring droughts, these practices are expected to increase farmers' ability to cope with shocks. One of the most common practices applied in the central and southern parts of Mali is contour bunding (CB). In this study the impact of the CB technology is evaluated with a focus on biophysical and socio-economic benefits. Data were collected in two agro-ecologies of southern Mali and were generated through field experimentation and household survey. Field experimentation involved implementation of contour lines with farm ridges, agronomic trails and runoff and erosion measurements. Agronomic data was collected on sorghum, maize, groundnut and millet for three consecutive years (2015 to 2017). Socio-economic data on the use of CB was obtained from individual farmer surveys. CB involves the layout of contour lines with land leveling devices to identify points of equal elevation and construction of contour lines with draught animals and human labor. The majority of the labor input to construct and maintain the CB comes from adult men who are head of the household (58%) and youth male (33%). Results indicate that with the application of CB yield of crops was higher with the highest increase in grain yield and biomass obtained for maize and millet (P < 0.01). CB application was useful in retaining soil water and reduced erosion rate. In treatment fields, 162 mm of rainfall per year was saved as soil moisture and on average 13,090 kg per hectare of soil was lost from farm fields without CB, and CB implementation significantly reduced the soil loss by 163% (P < 0.01). The improvements in crops yield and biomass, and the retention of soil nutrients positively changed farm level productivity conditions. The majority of farmers (78%) perceived higher income from the sale of crops grown on CB plots. These results suggest the landscape wide application of CB.
The joint impact of infrastructure and institutions on economic growth
Authors: Zergawu Yitagesu Zewdu , Walle Yabibal M. , Giménez-Gómez José-Manuel
Published: February 2020

This paper examines the joint impact of infrastructure capital and institutional quality on economic growth using a large panel dataset covering 99 countries and spanning the years 1980–2015. The empirical strategy involves estimating a simple growth model where, in addition to standard controls, infrastructure, institutional quality, and their interaction are included as explanatory variables. Potential endogeneity concerns are addressed by employing generalized method of moments estimators that utilize internal instruments. We find that the interaction terms between infrastructure capital and institutional quality show a positive and significant impact on economic growth. These results are robust to a variety of alternative specifications and institutional quality measures. Hence, our results suggest that maximizing returns from infrastructure capital requires improving the quality of institutions.
Prenatal alcohol exposure and developmental programming of mental illness
Authors: Burgess Danielle J. , Moritz Karen M.
Published: February 2020

It is well established that high-dose alcohol consumption during pregnancy increases the risk for a plethora of adverse offspring outcomes. These include neurodevelopmental, cognitive and social deficits, as well as psychiatric illnesses, such as depression and anxiety. However, much less evidence is available on the effects of low- and early-dose alcohol exposure on mental health outcomes, regardless of the accumulating evidence that mental health outcomes should be considered in the context of the Developmental Origins of Health and Disease hypothesis. This review will discuss the evidence that indicates low-dose and early prenatal alcohol exposure can increase the risk of mental illness in offspring and discuss the mechanistic pathways that may be involved.
New Methods for Linking Science Objectives to Remote Sensing Observations: A Concept Study Using Single‐ and Dual‐Pair Satellite Gravimetry Architectures
Authors: Hauk M. , Wiese D. N.
Published: February 2020

In this manuscript, we present a new analysis tool, called space‐time‐accuracy grid (STAG) analysis, to simultaneously assess the performance of an observing system architecture across space and time. Such an analysis tool is useful to directly link science objectives (typically expressed via a targeted spatial resolution, temporal resolution, and accuracy) to the expected performance of the observing system architecture. As a proof of concept, we apply STAG analysis to analyze three potential future observing systems for mass change in the Earth system: a single pair of polar orbiting satellites (heritage Gravity Recovery and Climate Experiment and Gravity Recovery and Climate Experiment Follow‐On), two polar pairs of satellites, and a polar pair of satellites coupled with an inclined (70°) pair of satellites. Here, we demonstrate the use of STAG analysis to quantify the relative performance of each architecture across space (200–1,800 km) and time (1–30 days), offering a significantly more comprehensive assessment of performance than previous studies. Results show that the polar pair coupled with the inclined pair reduces errors (after state‐of‐the‐art post‐processing for each architecture is accounted for) relative to the single pair of satellites by 40–60% in medium spatial scales (500–1,200 km), with the greatest benefit being for longer solution (monthly) timespans. Overall, the results from this case study highlight the importance of increasing the isotropy of the observable over simply increasing the sampling frequency. Some demonstrated benefits of STAG analysis include the ability to incorporate state‐of‐the‐art post‐processing methods into the analysis and also tailor the analysis to specific geographic regions to address targeted scientific objectives.
Refining Predictor Spectral Representation Using Wavelet Theory for Improved Natural System Modeling
Authors: Jiang Ze , Sharma Ashish , Johnson Fiona
Published: February 2020

Predicting future surpluses or shortages of water is a long‐standing problem having considerable ramifications to water management across the world. Any prediction model for a natural system such as one that estimates water surpluses or shortages requires a two‐step approach. These are the following: first, identify and select meaningful predictor variables from a large number of potential predictors and second, formulate an accurate, efficient, and robust predictive model between selected predictors and the response. Recognizing that the timescales at which a response may operate is usually different from that of the predictors being identified, we introduce here a wavelet‐based unique variance transformation to each of the multiple predictor variables in the system which ensures an improved regression relationship to the modeled response. All existing methods assume no change in predictors even if they characterize variability at markedly different timescales, a deficiency that is addressed using the variance‐transformed predictor which can explain maximal information in an associated response. Using this unique variance transformation, additional predictor variables can be selected by assessing their ability to characterize residual information in the response that accounts for the effect of preidentified predictors. We demonstrate the utility of the wavelet‐based method using synthetically generated data sets from known linear and nonlinear systems with parametric and nonparametric predictive models. Applications to a dynamic system and a real‐world example to downscale a drought indicator over the Sydney region confirm its utility in an applied setting.
New role of the antidepressant imipramine as a Fascin1 inhibitor in colorectal cancer cells
Authors: Alburquerque-González Begoña , Bernabé-García Manuel , Montoro-García Silvia , Bernabé-García Ángel , Rodrigues Priscila Campioni , Ruiz Sanz Javier , López-Calderón Fernando F. , Luque Irene , Nicolas Francisco José , Cayuela María Luisa , Salo Tuula , Pérez-Sánchez Horacio , Conesa-Zamora Pablo
Published: February 2020

Serrated adenocarcinoma (SAC) is more invasive, has worse outcomes than conventional colorectal carcinoma (CRC), and is characterized by frequent resistance to anti-epidermal growth factor receptor (EGFR) and overexpression of fascin1, a key protein in actin bundling that plays a causative role in tumor invasion and is overexpressed in different cancer types with poor prognosis. In silico screening of 9591 compounds, including 2037 approved by the Food and Drug Administration (FDA), was performed, and selected compounds were analyzed for their fascin1 binding affinity by differential scanning fluorescence. The results were compared with migrastatin as a typical fascin1 inhibitor. In silico screening and differential scanning fluorescence yielded the FDA-approved antidepressant imipramine as the most evident potential fascin1 blocker. Biophysical and different in vitro actin-bundling assays confirm this activity. Subsequent assays investigating lamellipodia formation and migration and invasion of colorectal cancer cells in vitro using 3D human tissue demonstrated anti-fascin1 and anti-invasive activities of imipramine. Furthermore, expression profiling suggests the activity of imipramine on the actin cytoskeleton. Moreover, in vivo studies using a zebrafish invasion model showed that imipramine is tolerated, its anti-invasive and antimetastatic activities are dose-dependent, and it is associated with both constitutive and induced fascin1 expression. This is the first study that demonstrates an antitumoral role of imipramine as a fascin1 inhibitor and constitutes a foundation for a molecular targeted therapy for SAC and other fascin1-overexpressing tumors.
Investigating the role of the innate immune response in relapse or blast crisis in chronic myeloid leukemia
Authors: Huang Weiqi , Liu Bin , Eklund Elizabeth A.
Published: February 2020

Chronic myeloid leukemia (CML) is characterized by expression of the tyrosine kinase oncogene, Bcr–abl. Tyrosine kinase inhibitors (TKI) induce prolonged remission in CML, and therapy discontinuation is an accepted approach to patients with reduction in Bcr–abl transcripts of four logs or greater. Half such individuals sustain a therapy free remission, but molecular mechanisms predicting relapse are undefined. We found relative calpain inhibition in CML cells with stabilization of calpain substrates, including βcatenin and Xiap1. Since the Survivin gene is activated by βcatenin, this identified two apoptosis-resistance mechanisms. We found that Survivin impaired apoptosis in leukemia stem cells (LSCs) and Xiap1 in CML granulocytes. Consistent with this, we determined treatment with an inhibitor of Survivin, but not Xiap1, prevented relapse during TKI treatment and after therapy discontinuation in a murine CML model. By transcriptome profiling, we identified activation of innate immune response pathways in murine CML bone marrow progenitors. This was increased by TKI treatment alone, but normalized with addition of a Survivin inhibitor. We found that activation of the innate immune response induced rapid blast crisis in untreated CML mice, and chronic phase relapse during a TKI discontinuation attempt. These results suggest that extrinsic stress exerts adverse effects on CML-LSCs.
Competition experiments in a soil microcosm reveal the impact of genetic and biotic factors on natural yeast populations
Authors: Bleuven Clara , Nguyen Guillaume Q , Després Philippe C , Filteau Marie , Landry Christian R
Published: February 2020

The ability to measure microbial fitness directly in natural conditions and in interaction with other microbes is a challenge that needs to be overcome if we want to gain a better understanding of microbial fitness determinants in nature. Here we investigate the influence of the natural microbial community on the relative fitness of the North American populations SpB, SpC and SpC* of the wild yeast Saccharomyces paradoxus using DNA barcodes and a soil microcosm derived from soil associated with oak trees. We find that variation in fitness among these genetically distinct groups is influenced by the microbial community. Altering the microbial community load and diversity with an irradiation treatment significantly diminishes the magnitude of fitness differences among populations. Our findings suggest that microbial interactions could affect the evolution of yeast lineages in nature by modulating variation in fitness.
Myotubularin-related protein 14 suppresses cardiac hypertrophy by inhibiting Akt
Authors: Zhang Jie-Lei , Zhang Dian-Hong , Li Ya-Peng , Wu Lei-Ming , Liang Cui , Yao Rui , Wang Zheng , Feng Sheng-dong , Wang Zhong-Min , Zhang Yan-Zhou
Published: February 2020

Cardiac hypertrophy (CH) is an independent risk factor for many cardiovascular diseases, and is one of the primary causes of morbidity and mortality in elderly people. Pathological CH involves excessive protein synthesis, increased cardiomyocyte size, and ultimately the development of heart failure. Myotubularin-related protein 14 (MTMR14) is a member of the myotubularin (MTM)-related protein family, which is involved in apoptosis, aging, inflammation, and autophagy. However, its exact function in CH is still unclear. Herein, we investigated the roles of MTMR14 in CH. We show that MTMR14 expression was increased in hypertrophic mouse hearts. Mice deficient in heart MTMR14 exhibited an aggravated aortic-banding (AB)-induced CH phenotype. In contrast, MTMR14 overexpression prevented pressure overload-induced hypertrophy. At the molecular level, prevention of CH in the absence of MTMR14 involved elevations in Akt pathway components, which are key elements that regulate apoptosis and cell proliferation. These results demonstrate that MTMR14 is a new molecular target for the treatment of CH.
Collaborative interactions of heterogenous ribonucleoproteins contribute to transcriptional regulation of sterol metabolism in mice
Authors: Zhang Zhengyi , Feng An-Chieh , Salisbury David , Liu Xin , Wu Xiaohui , Kim Jason , Lapina Irina , Wang Dan , Lee Brennan , Fraga Josue , Pan Calvin , Williams Kevin J. , Lusis Aldons J. , Scumpia Phil , Sallam Tamer
Published: February 2020

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are a group of functionally versatile proteins that play critical roles in the biogenesis, cellular localization and transport of RNA. Here, we outline a role for hnRNPs in gene regulatory circuits controlling sterol homeostasis. Specifically, we find that tissue-selective loss of the conserved hnRNP RALY enriches for metabolic pathways. Liver-specific deletion of RALY alters hepatic lipid content and serum cholesterol level. In vivo interrogation of chromatin architecture and genome-wide RALY-binding pattern reveal insights into its cooperative interactions and mode of action in regulating cholesterogenesis. Interestingly, we find that RALY binds the promoter region of the master metabolic regulator Srebp2 and show that it directly interacts with coactivator Nuclear Transcription Factor Y (NFY) to influence cholesterogenic gene expression. Our work offers insights into mechanisms orchestrating selective promoter activation in metabolic control and a model by which hnRNPs can impact health and disease states.
Pan-cancer analysis reveals cooperativity of both strands of microRNA that regulate tumorigenesis and patient survival
Authors: Mitra Ramkrishna , Adams Clare M. , Jiang Wei , Greenawalt Evan , Eischen Christine M.
Published: February 2020

Recently, both 5p and 3p miRNA strands are being recognized as functional instead of only one, leaving many miRNA strands uninvestigated. To determine whether both miRNA strands, which have different mRNA-targeting sequences, cooperate to regulate pathways/functions across cancer types, we evaluate genomic, epigenetic, and molecular profiles of >5200 patient samples from 14 different cancers, and RNA interference and CRISPR screens in 290 cancer cell lines. We identify concordantly dysregulated miRNA 5p/3p pairs that coordinately modulate oncogenic pathways and/or cell survival/growth across cancers. Down-regulation of both strands of miR-30a and miR-145 recurrently increased cell cycle pathway genes and significantly reduced patient survival in multiple cancers. Forced expression of all four strands show cooperativity, reducing cell cycle pathways and inhibiting lung cancer cell proliferation and migration. Therefore, we identify miRNA whose 5p/3p strands function together to regulate core tumorigenic processes/pathways and reveal a previously unknown pan-cancer miRNA signature with patient prognostic power.
Relaxed sequence constraints favor mutational freedom in idiosyncratic metazoan mitochondrial tRNAs
Authors: Kuhle Bernhard , Chihade Joseph , Schimmel Paul
Published: February 2020

Metazoan complexity and life-style depend on the bioenergetic potential of mitochondria. However, higher aerobic activity and genetic drift impose strong mutation pressure and risk of irreversible fitness decline in mitochondrial (mt)DNA-encoded genes. Bilaterian mitochondria-encoded tRNA genes, key players in mitochondrial activity, have accumulated mutations at significantly higher rates than their cytoplasmic counterparts, resulting in foreshortened and fragile structures. Here we show that fragility of mt tRNAs coincided with the evolution of bilaterian animals. We demonstrate that bilaterians compensated for this reduced structural complexity in mt tRNAs by sequence-independent induced-fit adaption to the cognate mitochondrial aminoacyl-tRNA synthetase (aaRS). Structural readout by nuclear-encoded aaRS partners relaxed the sequence constraints on mt tRNAs and facilitated accommodation of functionally disruptive mutational insults by cis-acting epistatic compensations. Our results thus suggest that mutational freedom in mt tRNA genes is an adaptation to increased mutation pressure that was associated with the evolution of animal complexity.
A serine/threonine protein kinase encoding gene KERNEL NUMBER PER ROW6 regulates maize grain yield
Authors: Jia Haitao , Li Manfei , Li Weiya , Liu Lei , Jian Yinan , Yang Zhixing , Shen Xiaomeng , Ning Qiang , Du Yanfang , Zhao Ran , Jackson David , Yang Xiaohong , Zhang Zuxin
Published: February 2020

Increasing grain yield of maize (Zea maysL.) is required to meet the rapidly expanding demands for maize-derived food, feed, and fuel. Breeders have enhanced grain productivity of maize hybrids by pyramiding desirable characteristics for larger ears. However, loci selected for improving grain productivity remain largely unclear. Here, we show that a serine/threonine protein kinase encoding geneKERNEL NUMBER PER ROW6 (KNR6)determines pistillate floret number and ear length. Overexpression ofKNR6or introgression of alleles lacking the insertions of two transposable elements in the regulatory region ofKNR6can significantly enhance grain yield. Further in vitro evidences indicate that KNR6 can interact with an Arf GTPase-activating protein (AGAP) and its phosphorylation by KNR6 may affect ear length and kernel number. This finding provides knowledge basis to enhance maize hybrids grain yield.
Prevention of aspartimide formation during peptide synthesis using cyanosulfurylides as carboxylic acid-protecting groups
Authors: Neumann Kevin , Farnung Jakob , Baldauf Simon , Bode Jeffrey W.
Published: February 2020

Although peptide chemistry has made great progress, the frequent occurrence of aspartimide formation during peptide synthesis remains a formidable challenge. Aspartimide formation leads to low yields in addition to costly purification or even inaccessible peptide sequences. Here, we report an alternative approach to address this longstanding challenge of peptide synthesis by utilizing cyanosulfurylides to mask carboxylic acids by a stable C–C bond. These functional groups—formally zwitterionic species—are exceptionally stable to all common manipulations and impart improved solubility during synthesis. Deprotection is readily and rapidly achieved under aqueous conditions with electrophilic halogenating agents via a highly selective C–C bond cleavage reaction. This protecting group is employed for the synthesis of a range of peptides and proteins including teduglutide, ubiquitin, and the low-density lipoprotein class A. This protecting group strategy has the potential to overcome one of the most difficult aspects of modern peptide chemistry.
Microglia control vascular architecture via a TGFβ1 dependent paracrine mechanism linked to tissue mechanics
Authors: Dudiki Tejasvi , Meller Julia , Mahajan Gautam , Liu Huan , Zhevlakova Irina , Stefl Samantha , Witherow Conner , Podrez Eugene , Kothapalli Chandrasekhar R. , Byzova Tatiana V.
Published: February 2020

Tissue microarchitecture and mechanics are important in development and pathologies of the Central Nervous System (CNS); however, their coordinating mechanisms are unclear. Here, we report that during colonization of the retina, microglia contacts the deep layer of high stiffness, which coincides with microglial bipolarization, reduction in TGFβ1 signaling and termination of vascular growth. Likewise, stiff substrates induce microglial bipolarization and diminish TGFβ1 expression in hydrogels. Both microglial bipolarization in vivo and the responses to stiff substrates in vitro require intracellular adaptor Kindlin3 but not microglial integrins. Lack of Kindlin3 causes high microglial contractility, dysregulation of ERK signaling, excessive TGFβ1 expression and abnormally-patterned vasculature with severe malformations in the area of photoreceptors. Both excessive TGFβ1 signaling and vascular defects caused by Kindlin3-deficient microglia are rescued by either microglial depletion or microglial knockout of TGFβ1 in vivo. This mechanism underlies an interplay between microglia, vascular patterning and tissue mechanics within the CNS.