bluuebunny/crossref_metadata_2025 huggingface dataset:
Why Epistemic Reductionism Won’t Save the Moral Error Theorist
Authors: Murphy Alex
Published: January 2020

Moral error theorists often respond to the epistemic companions in guilt strategy by adopting the Disparity Response: reject the putative parity between moral and epistemic reasons and claim that though the former are irreducibly normative, the latter aren’t. I argue such a response fails. Expanding on Das’ Australas J Philos 95(1):58–69, (2017) work I present a master argument against Disparity Responses: the arguments moral error theorists use to advance their conceptual claim apply in the epistemic domain also. This prohibits the error theorist from adopting epistemic reductionism. I use Jonas Olson’s work as exemplary of moral error theory. I demonstrate that Olson’s (2014) argument that the rhetorical authority of moral claims is best explained by the error theorist’s conceptual claim applies equally in the epistemic case. Olson (2018) attempts to avoid this by claiming that epistemic claims are reducible to claims about whether our doxastic attitudes live up to their functions. There are two problems with Olson’s (2018) argument. Firstly, functional reasons are a species of a common genus – standards reasons – and since Olson’s authority argument against moral reductionism applies to standards reasons, it applies to functional reasons. Secondly, Olson’s (2018) claim that we cannot also cast moral reasons as functional is under-supported. I suggest that there is plausible evidence that we can and undermine his arguments against this claim. I do not argue that the epistemic companions in guilt strategy demonstrates the falsity of moral error theory. Rather, I argue that the Disparity Response to the epistemic companions in guilt strategy fails.
Conformational analysis of macrocycles: comparing general and specialized methods
Authors: Olanders Gustav , Alogheli Hiba , Brandt Peter , Karlén Anders
Published: January 2020

Macrocycles represent an important class of medicinally relevant small molecules due to their interesting biological properties. Therefore, a firm understanding of their conformational preferences is important for drug design. Given the importance of macrocycle-protein modelling in drug discovery, we envisaged that a systematic study of both classical and recent specialized methods would provide guidance for other practitioners within the field. In this study we compare the performance of the general, well established conformational analysis methods Monte Carlo Multiple Minimum (MCMM) and Mixed Torsional/Low-Mode sampling (MTLMOD) with two more recent and specialized macrocycle sampling techniques: MacroModel macrocycle Baseline Search (MD/LLMOD) and Prime macrocycle conformational sampling (PRIME-MCS). Using macrocycles extracted from 44 macrocycle-protein X-ray crystallography complexes, we evaluated each method based on their ability to (i) generate unique conformers, (ii) generate unique macrocycle ring conformations, (iii) identify the global energy minimum, (iv) identify conformers similar to the X-ray ligand conformation after Protein Preparation Wizard treatment (X-rayppw), and (v) to the X-rayppwring conformation. Computational speed was also considered. In addition, conformational coverage, as defined by the number of conformations identified, was studied. In order to study the relative energies of the bioactive conformations, the energy differences between the global energy minima and the energy minimized X-rayppwstructures and, the global energy minima and the MCMM-Exhaustive (1,000,000 search steps) generated conformers closest to the X-rayppwstructure, were calculated and analysed. All searches were performed using relatively short run times (10,000 steps for MCMM, MTLMOD and MD/LLMOD). To assess the performance of the methods, they were compared to an exhaustive MCMM search using 1,000,000 search steps for each of the 44 macrocycles (requiring ca 200 times more CPU time). Prior to our analysis, we also investigated if the general search methods MCMM and MTLMOD could also be optimized for macrocycle conformational sampling. Taken together, our work concludes that the more general methods can be optimized for macrocycle modelling by slightly adjusting the settings around the ring closure bond. In most cases, MCMM and MTLMOD with either standard or enhanced settings performed well in comparison to the more specialized macrocycle sampling methods MD/LLMOD and PRIME-MCS. When using enhanced settings for MCMM and MTLMOD, the X-rayppwconformation was regenerated with the greatest accuracy. The, MD/LLMOD emerged as the most efficient method for generating the global energy minima.

Graphic abstract
Stress Echocardiography in the Era of Fractional Flow Reserve
Authors: Bioh Gabriel , Senior Roxy
Published: January 2020

Purpose of Review

It is the aim of this review to demonstrate the relevance of stress echocardiography in the era of fractional flow reserve by establishing the current use of stress echocardiography and fractional flow reserve, underlining their physiological basis and through this demonstrating the clear differences in their application.

Recent Findings

The importance of the microcirculation is only now being understood, no more so than in the fact that abnormalities in the microcirculation, determined by abnormal coronary flow reserve, predict adverse mortality regardless of the normality of the epicardial coronary lesions. Stress echocardiography therefore gives a fuller picture of the overall cardiovascular risk to our patients in its ability to interrogate the epicardial vessels down to the microcirculation, with a number of techniques available to measure coronary flow reserve such as myocardial perfusion stress echocardiography and transthoracic Doppler stress echocardiography of epicardial coronary vessels. Fractional flow reserve can then add further information by determining whether a coronary artery lesion is responsible for myocardial ischaemia.

In an era of fractional flow reserve affording the resolution of myocardial ischaemia down to the specific lesion, it can be tempting to think that other generally non-invasive techniques no longer have a role in the investigation and management of coronary artery disease. This, however, betrays a lack of understanding of the scope and complexity of coronary artery disease from epicardial vessels down to the microvasculature, the physiological basis of the tests available and therefore what, in fact, is actually being measured. For some, fractional flow reserve is held as a gold standard by which to compare other techniques such as stress echocardiography as correct or incorrect. However, these tests do not measure the same thing, and therefore, they cannot be directly compared. Stress echocardiography gives a fuller picture through its ability to account for the coronary flow reserve, considering the epicardial vessels down to the microvasculature. Fractional flow reserve is far more specific, looking at the effect of the lesion being interrogated. Furthermore, where fractional flow reserve is normal, we now know that knowledge of the coronary flow reserve is critical as it is this that allows us to predict the overall mortality risk of our patient. We therefore require a combination of the two techniques.
Economic patterns in a world with artificial intelligence
Authors: Wagner Dirk Nicolas
Published: January 2020

This article outlines relevant economic patterns in a world with artificial intelligence (AI). Five specific economic patterns influenced by AI are discussed: (1) following in the footsteps of ‘homo economicus’ a new type of agent, ‘machina economica’, enters the stage of the global economy. (2) The pattern of division of labor and specialization is further accelerated by AI-induced micro-division of labor. (3) The introduction of AI leads to triangular agency relationships and next level information asymmetries. (4) Data and AI-based machine labor have to be understood as new factors of production. (5) The economics of AI networks can lead to market dominance and unwanted external effects. The analytical perspective is rooted in institutional economics and serves to integrate findings from relevant disciplines in economics and computer science. It is based on the research proposition that ‘institutional matters’ are of high relevance also in a world with AI but that AI gives a new meaning to these matters. The discussion unveils a reinforcing interdependence of the patterns portrayed and points to required research.
Operational technology security – a data perspective
Authors: Andreu Andres
Published: January 2020

In the evolution of the operational technology (OT) and Industrial Internet of Things (IIoT) landscapes, one of the most commonly overlooked areas within cyber security is that of the actual values in the data. Contextually this means that when the term ‘data’ is used, the reference is to data seen beyond network metadata (ie, source address, source port, destination address, destination port, etc).

With operational technology (OT) and the Industrial Internet of Things (IIoT), one of the most commonly overlooked security issues is the values in the data.

The primary concern is the data elements that actually have an impact on the physical realm via values being set or modified. The objective is to not allow a hostile piece of data (ie, a value change) to reach a destination endpoint, such as a programmable logic controller (PLC), causing a negative physical action. Andres Andreu of Bayshore Networks argues that we need to have a deeper understanding of this data if we are to properly secure such environments.
Autoregressive repeatability model for genetic evaluation of longitudinal reproductive traits in dairy cattle
Authors: Silva Hugo T. , Lopes Paulo S. , Costa Claudio N. , Silva Fabyano F. , Silva Delvan A. , Silva Alessandra A. , Thompson Gertrude , Carvalheira Júlio
Published: January 2020

We investigated the efficiency of the autoregressive repeatability model (AR) for genetic evaluation of longitudinal reproductive traits in Portuguese Holstein cattle and compared the results with those from the conventional repeatability model (REP). The data set comprised records taken during the first four calving orders, corresponding to a total of 416, 766, 872 and 766 thousand records for interval between calving to first service, days open, calving interval and daughter pregnancy rate, respectively. Both models included fixed (month and age classes associated to each calving order) and random (herd-year-season, animal and permanent environmental) effects. For AR model, a first-order autoregressive (co)variance structure was fitted for the herd-year-season and permanent environmental effects. The AR outperformed the REP model, with lower Akaike Information Criteria, lower Mean Square Error and Akaike Weights close to unity. Rank correlations between estimated breeding values (EBV) with AR and REP models ranged from 0.95 to 0.97 for all studied reproductive traits, when the total bulls were considered. When considering only the top-100 selected bulls, the rank correlation ranged from 0.72 to 0.88. These results indicate that the re-ranking observed at the top level will provide more opportunities for selecting the best bulls. The EBV reliabilities provided by AR model was larger for all traits, but the magnitudes of the annual genetic progress were similar between two models. Overall, the proposed AR model was suitable for genetic evaluations of longitudinal reproductive traits in dairy cattle, outperforming the REP model.
A new species ofPseudoacanthocephalus(Acanthocephala: Echinorhynchidae) from the guttural toad,Sclerophrys gutturalis(Bufonidae), introduced into Mauritius, with comments on the implications of the introductions of toads and their parasites into the UK
Authors: Smales L.R. , Allain S.J.R. , Wilkinson J.W. , Harris E.
Published: January 2020

Pseudoacanthocephalus goodmanin. sp. is described from faecal pellets collected fromSclerophrys gutturalis(Power, 1927), the guttural toad. The species is characterized by a suite of characters, including a proboscis armature of 14–18 longitudinal rows of 4–6 hooks with simple roots, lemnisci longer than the proboscis receptacle, equatorial testes, a cluster of elongated cement glands and eggs without polar prolongations of the middle membrane 72.6–85.8 long. The toad had been accidentally translocated from Mauritius to the UK in a tourist's luggage and survived a washing machine cycle. The guttural toad was introduced into Mauritius from South Africa in 1922 and the cane toad,Rhinella marina(Linneaus, 1758), from South America, between 1936 and 1938. It seems most likely, therefore, thatP. goodmaniwas introduced, with the guttural toad, from South Africa. The cane toad is host to the similar species,Pseudoacanthocephalus lutzi, from the Americas, butP. lutzihas not been recorded from places where the cane toad has been introduced elsewhere. Clearly, the guttural toad is a hardy and adaptable species, although it seems unlikely that it could become established in Northern Europe. Nevertheless, any accidental translocation of hosts poses the potential risk of introducing unwanted pathogens into the environment and should be guarded against.
Free Heyting algebra endomorphisms: Ruitenburg’s Theorem and beyond
Authors: Ghilardi Silvio , Santocanale Luigi
Published: January 2020

Ruitenburg’s Theorem says that every endomorphismfof a finitely generated free Heyting algebra is ultimately periodic ifffixes all the generators but one. More precisely, there isN≥ 0 such thatfN+2=fN, thus the period equals 2. We give a semantic proof of this theorem, using duality techniques and bounded bisimulation ranks. By the same techniques, we tackle investigation of arbitrary endomorphisms of free algebras. We show that they are not, in general, ultimately periodic. Yet, when they are (e.g. in the case of locally finite subvarieties), the period can be explicitly bounded as function of the cardinality of the set of generators.
How different code-switching types modulate bilinguals’ executive functions: A dual control mode perspective
Authors: Hofweber Julia , Marinis Theodoros , Treffers-Daller Jeanine
Published: January 2020

Most existing studies on the relationship between code-switching and executive functions have focused on experimentally induced language-switching, which differs fundamentally from naturalistic code-switching. This study investigated whether and how bilinguals’ code-switching practices modulate different aspects of executive functioning. Our findings suggest that existing processing models of code-switching should be extended by a dual control mode perspective, differentiating between reactive and proactive monitoring. Bilinguals engaging in code-switching types that keep languages more separate (Alternation) displayed inhibitory advantages in a flanker task inducing reactive control. Dense code-switching, which requires bilinguals to constantly monitor cross-linguistic competition, explained performance in proactive monitoring conditions. Furthermore, a correlation between Dense code-switching and response inhibition suggests that linguistic co-activation may persist during articulatory stages of language processing. Crucially, bilinguals outperformed monolinguals at those aspects of the executive system that were trained by their most frequent code-switching habits. This underlines the importance of sociolinguistic variables in bilingualism research.
Azimuthal Anisotropy of the North American Upper Mantle Based on Full Waveform Inversion
Authors: Zhu Hejun , Yang Jidong , Li Xueyan
Published: January 2020

A new azimuthal anisotropy model for the North American and Caribbean Plates, namely,
, is constructed based on full waveform inversion and records from the USArray and other temporary/permanent networks deployed in the study region. A total of 180 earthquakes and 4,516 seismographic stations are employed in the inversion to simultaneously constrain radially and azimuthally anisotropic model parameters:
,
,
, and
, within the crust and mantle. Thirty‐two preconditioned conjugate gradient iterations have been utilized to minimize frequency‐dependent phase discrepancies between observed and predicted seismograms for three‐component short‐period (15–40 s) body waves and long‐period (25–100 s) surface waves. Model
exhibits complicated variations in anisotropic fabrics underneath the western and eastern United States, especially at depths shallower than 100 km. For instance, the fast axis orientations in model
suggest the presence of trench‐perpendicular mantle flows underneath the Cascadia Subduction Zone and also follow the strikes of the Snake River Plain, the Ouachita Orogenic Front, and the Grenville and Appalachian Orogenic Belts. The amplitudes of azimuthal anisotropy reduce to around 1% at depths greater than 200 km, and the orientations are subparallel to the global plate motion directions to the east of the Rocky Mountain, except for large discrepancies in central and eastern Canada. At a depth of 700 km, the fast axes change along the trajectory of the Farallon slab underneath the Great Lakes region and Gulf of Mexico, which might indicate the development of 2‐D poloidal‐mode mantle flows perpendicular to the strike of the sinking slab within the uppermost lower mantle. Comparisons between model
with a western U.S. model from ambient noise tomography and SKS splitting measurements demonstrate a relatively good agreement for the fast axis orientations, considering the usage of different data sets and imaging techniques. However, the absolute magnitude of azimuthal anisotropy in model
might be underestimated, especially at greater depths, given the poor agreement on the amplitudes of predicted and observed SKS splitting times. At the current stage, the agreement among different azimuthal anisotropy models at global and continental scales is still poor even for the United States with a dense station coverage.
Constraints on the Geometry and Frictional Properties of the Main Himalayan Thrust Using Coseismic, Postseismic, and Interseismic Deformation in Nepal
Authors: Ingleby T. , Wright T. J. , Hooper A. , Craig T. J. , Elliott J. R.
Published: January 2020

The geometry and frictional properties of a fault system are key parameters required to understand its seismic behavior. The Main Himalayan Thrust in Nepal is the type example of a continental megathrust and forms part of a fault system which accommodates a significant fraction of India‐Eurasia convergence. Despite extensive study of this zone of shortening, the geometry of the fault system remains controversial. Here, we use interseismic, coseismic, and postseismic geodetic data in Nepal to investigate the proposed downdip geometries. We use interseismic and coseismic data from previous studies, acquired before and during the 2015
 7.8 Gorkha earthquake. We then supplement these by processing our own postseismic deformation data, acquired following the Gorkha earthquake. We find that kinematic modeling of geodetic data alone cannot easily distinguish between the previously proposed geometries. We therefore develop a mechanical joint coseismic‐postseismic slip inversion which simultaneously solves for the distribution of coseismic slip and rate‐strengthening friction parameters. We run this inversion using the proposed geometries and find that they are all capable of explaining the majority of geodetic data. We find values for the rate parameter,
, from the rate‐and‐state friction law that are between 0.8 and
, depending on the geometry used. These values are in agreement with results from laboratory studies and those inferred from other earthquakes. We suggest that the limitations of earthquake cycle geodesy partly explain the continued controversy over the geometry and role of various faults in the Nepal Himalaya.
Marine X‐Band Radar Currents and Bathymetry: An Argument for a Wave Number‐Dependent Retrieval Method
Authors: Lund B. , Haus B. K. , Graber H. C. , Horstmann J. , Carrasco R. , Novelli G. , Guigand C. M. , Mehta S. , Laxague N. J. M. , Özgökmen T. M.
Published: January 2020

This study evaluates shipboard marine X‐band radar (MR) near‐surface current and bathymetry measurements under shallow water conditions. The retrieval algorithm is based on the surface wave signal within three‐dimensional wave number frequency MR backscatter intensity variance spectra. The MR data were collected during a research cruise that investigated submesoscale processes and their impact on oil spill transport in the Louisiana Bight. The MR currents and bathymetry are validated using measurements from 500 GPS‐equipped surface drifters, a shipboard acoustic Doppler current profiler, and a shipboard single‐beam echo sounder. Earlier results from the same experiment but using a different set of sensors indicate strong upper ocean vertical current shear over a 3.5 hr period, despite only mild wind forcing. Here, the MR currents are derived as a function of wave number, providing a measure of vertical shear for the full duration of the cruise. Strong vertical shear is frequently observed, with a maximum difference of 0.42 m/s between the MR high (effective depth of
0.9 m) and low (
2.4 m) wave number bins. Treating the drifter and echo sounder measurements as truth, the accuracies of the MR near‐surface currents and bathymetry are 0.04–0.07 m/s and 1.2 m (or 7% of the mean water depth). However, it is shown that
50% of the MR high wave number and drifter current differences is due to vertical shear. The shallow water MR near‐surface current accuracy thus matches findings from a previous deep water validation where vertical shear was much weaker.
Observational Evidence of Surface Wave‐Generated Strong Ocean Turbulence
Authors: Ma Hongyu , Dai Dejun , Guo Jingsong , Qiao Fangli
Published: January 2020

By using an acoustic Doppler velocimeter mounted on the seabed of the continental shelf of the northern South China Sea, high frequency velocity fluctuations were measured for 4.5 days. The turbulent kinetic energy dissipation rate was estimated. During the observation, the strong ocean response to Typhoon Rammasun was recorded to compare the turbulent characteristics before and during the typhoon. The results show that the turbulence near the seabed is mainly generated by the tidal current shear and exhibits a quarter diurnal variation during the period before the typhoon. During the typhoon period, the dissipation rate ε dramatically increased from 1 × 10−6 to 1 × 10−2 m2 s−3 within a short time, and the significant wave height and the surface wave orbital velocity showed the same tendency. This finding suggests that the turbulence is dominantly generated by the surface waves near the seabed.
A Ray Tracing Simulation of HF Ionospheric Radar Performance at African Equatorial Latitudes
Authors: Michael Chizurumoke M. , Yeoman Tim K. , Wright Darren M. , Milan Steve E. , James Matthew K.
Published: January 2020

High‐frequency (HF) coherent radars are widely applied for studying electrodynamic processes in the Earth's upper atmosphere and ionosphere. Super Dual Auroral Radar Network (SuperDARN) is an international network of such radars located at high‐ and middle‐latitude regions in the Northern and Southern Hemispheres. A major criterion of the HF coherent radar technique entails that the HF waves propagate orthogonal to the geomagnetic field lines (aspect angle
1°) in the ionospheric irregularity region from where backscatter originates. In this paper we present an HF ray tracing simulation of the performance of three proposed equatorial HF radar systems for the African equatorial sector. We use a number of realistic average ionospheres deduced from the International Reference Ionosphere (IRI) 2012 model and magnetic field geometries from the International Geomagnetic Reference Field (IGRF) to determine likely propagation paths and orthogonality conditions for such radar systems. The east‐west azimuth (
25° range) has a significant likelihood of achieving a SuperDARN‐type backscatter in the African equatorial sector, mainly due to the prevailing magnetic field geometry. This analysis provides a feasibility study for developing a SuperDARN‐like radar for studying the equatorial ionosphere over the African longitude sector, for example, in determining the technical radar characteristics such as preferable operating frequencies, antenna boresight orientation, and azimuth coverage and provides a simulation of the expected localization of radar backscatter as a function of radar location and beam direction, as well as the time of day, season, and sunspot number.
Water Table Depth and Soil Salinization: From Pore‐Scale Processes to Field‐Scale Responses
Authors: Shokri‐Kuehni Salomé M. S. , Raaijmakers Bernadette , Kurz Theresa , Or Dani , Helmig Rainer , Shokri Nima
Published: January 2020

The accumulation of salts in soils adversely influences plant growth and biological activity resulting in loss of yields and soil ecosystem services. Water table depth plays an important role on solute distribution through the unsaturated zone. We focus on the relationship between saline water evaporation from soil surfaces and water table depths. When the water table was hydraulically connected to the surface, we found more evaporatively driven sodium chloride precipitation at the surface with deeper water tables relative to shallow ones. We attribute this result to lower surface water contents that reach solubility limit sooner and support an expanding salt crust. Thermal imaging confirmed that when surface is hydraulically connected to the water table, capillary flows through the porous precipitated salt maintain the evaporative flux. Macroscopic continuum‐scale numerical simulations demonstrate higher solute concentration closer to the surface in the case of deeper water tables supporting the microscopic picture attributed to fewer evaporation and solute deposition sites at the surface with deeper water tables. Insights from the laboratory‐scale experiments and numerical studies were used to describe soil salinity at much larger scales. We employed two global‐scale databases for topsoil salinity, soil texture, and water table depths to link our laboratory‐scale findings with long‐term and field‐scale observations. The results illustrate the importance of pore‐scale physics and processes on constraining the field‐scale responses.
Genetic variants in CYP2A6 and UGT1A9 genes associated with urinary nicotine metabolites in young Mexican smokers
Authors: Borrego-Soto Gissela , Perez-Paramo Yadira X. , Chen Gang , Santuario-Facio Sandra K. , Santos-Guzman Jesus , Posadas-Valay Rodolfo , Alvarado-Monroy Fatima M. , Balderas-Renteria Isaias , Medina-Gonzalez Ramses , Ortiz-Lopez Rocio , Lazarus Philip , Rojas-Martinez Augusto
Published: January 2020

Nicotine is the major pharmacologically active substance in tobacco. Several studies have examined genotypes related to nicotine metabolism, but few studies have been performed in the Mexican population. The objective was to identify associations between gene variants in metabolizing enzymes and the urinary levels of nicotine metabolites among Mexican smokers. The levels of nicotine and its metabolites were determined in the urine of 88 young smokers from Mexico, and 167 variants in 24 genes associated with nicotine metabolism were genotyped by next-generation sequencing (NGS). Trans-3′-hydroxy-cotinine (3HC) and 4-hydroxy-4-(3-pyridyl)-butanoic acid were the most abundant metabolites (35 and 17%, respectively). CYP2A6*12 was associated with 3HC (p = 0.014). The rs145014075 was associated with creatinine-adjusted levels of nicotine (p = 0.035), while the rs12471326 (UGT1A9) was associated to cotinine-N-glucuronide (p = 0.030). CYP2A6 and UGT1A9 variants are associated to nicotine metabolism. 4HPBA metabolite was an abundant urinary metabolite in young Mexican smokers.
Golgi organization is regulated by proteasomal degradation
Authors: Eisenberg-Lerner Avital , Benyair Ron , Hizkiahou Noa , Nudel Neta , Maor Roey , Kramer Matthias P. , Shmueli Merav D. , Zigdon Inbal , Cherniavsky Lev Marina , Ulman Adi , Sagiv Jitka Yehudith , Dayan Molly , Dassa Bareket , Rosenwald Mercedes , Shachar Idit , Li Jie , Wang Yanzhuang , Dezorella Nili , Khan Suman , Porat Ziv , Shimoni Eyal , Avinoam Ori , Merbl Yifat
Published: January 2020

The Golgi is a dynamic organelle whose correct assembly is crucial for cellular homeostasis. Perturbations in Golgi structure are associated with numerous disorders from neurodegeneration to cancer. However, whether and how dispersal of the Golgi apparatus is actively regulated under stress, and the consequences of Golgi dispersal, remain unknown. Here we demonstrate that 26S proteasomes are associated with the cytosolic surface of Golgi membranes to facilitate Golgi Apparatus-Related Degradation (GARD) and degradation of GM130 in response to Golgi stress. The degradation of GM130 is dependent on p97/VCP and 26S proteasomes, and required for Golgi dispersal. Finally, we show that perturbation of Golgi homeostasis induces cell death of multiple myeloma in vitro and in vivo, offering a therapeutic strategy for this malignancy. Taken together, this work reveals a mechanism of Golgi-localized proteasomal degradation, providing a functional link between proteostasis control and Golgi architecture, which may be critical in various secretion-related pathologies.
Photonic integrated field-programmable disk array signal processor
Authors: Zhang Weifeng , Yao Jianping
Published: January 2020

Thanks to the nature of strong programmability, field-programmable gate arrays (FPGAs) have been playing a significant role in signal processing and control. With the explosive growth in digital data, big data analytics becomes an important emerging field, in which FPGAs are a major player. However, the computational speed and power efficiency provided by FPGAs are limited by electronic clock rates and Ohmic losses. To overcome the limitations, photonics is envisioned as an enabling solution, thanks to its ultrafast and low power consumption feature. In this paper, we propose a scalable photonic field-programmable disk array (FPDA) signal processor. Ultra-compact microdisk resonators are leveraged as a fundamental execution units in the core to route, store and process optical signals. By field-programming the processor, diverse circuit topologies can be realized to perform multiple specific signal processing functions including filtering, temporal differentiation, time delay, beamforming, and spectral shaping.
Interplay of water and a supramolecular capsule for catalysis of reductive elimination reaction from gold
Authors: Welborn Valerie Vaissier , Li Wan-Lu , Head-Gordon Teresa
Published: January 2020

Supramolecular assemblies have gained tremendous attention due to their ability to catalyze reactions with the efficiencies of natural enzymes. Using ab initio molecular dynamics, we identify the origin of the catalysis by the supramolecular capsule Ga4L612− on the reductive elimination reaction from gold complexes and assess their similarity to natural enzymes. By comparing the free energies of the reactants and transition states for the catalyzed and uncatalyzed reactions, we determine that an encapsulated water molecule generates electric fields that contributes the most to the reduction in the activation free energy. Although this is unlike the biomimetic scenario of catalysis through direct host-guest interactions, the electric fields from the nanocage also supports the transition state to complete the reductive elimination reaction with greater catalytic efficiency. However it is also shown that the nanocage poorly organizes the interfacial water, which in turn creates electric fields that misalign with the breaking bonds of the substrate, thus identifying new opportunities for catalytic design improvements in nanocage assemblies.
The first high-resolution meteorological forcing dataset for land process studies over China
Authors: He Jie , Yang Kun , Tang Wenjun , Lu Hui , Qin Jun , Chen Yingying , Li Xin
Published: January 2020

The China Meteorological Forcing Dataset (CMFD) is the first high spatial-temporal resolution gridded near-surface meteorological dataset developed specifically for studies of land surface processes in China. The dataset was made through fusion of remote sensing products, reanalysis datasets and in-situ station data. Its record begins in January 1979 and is ongoing (currently up to December 2018) with a temporal resolution of three hours and a spatial resolution of 0.1°. Seven near-surface meteorological elements are provided in the CMFD, including 2-meter air temperature, surface pressure, and specific humidity, 10-meter wind speed, downward shortwave radiation, downward longwave radiation and precipitation rate. Validations against observations measured at independent stations show that the CMFD is of superior quality than the GLDAS (Global Land Data Assimilation System); this is because a larger number of stations are used to generate the CMFD than are utilised in the GLDAS. Due to its continuous temporal coverage and consistent quality, the CMFD is one of the most widely-used climate datasets for China.
A genetic development route analysis on MDS subset carrying initial epigenetic gene mutations
Authors: Li Xiao , Xu Feng , Wu Ling-Yun , Zhao You-Shan , Guo Juan , He Qi , Zhang Zheng , Chang Chun-Kang , Wu Dong
Published: January 2020

MDS development is a dynamic process during which the accumulation of somatic mutations leads to specific malignant evolution. To elucidate the differential roles of gene mutations in typical MDS, we used targeted sequencing to investigate clonal patterns from 563 patients and focused on cases (199/563 cases) with initial mutations (ASXL1, DNMT3A and TET2) at MDS diagnosis. The consistency of frequency and distribution in patients with or without aberrant chromosomes suggested early events of these initial mutations. Some additional driver mutations (SF3B1, U2AF1 or RUNX1) played roles to keep the basic disease features, or give rise to different phenotypes (BCOR, EZH2 or TP53) in individual patients. Notably, analysis in paired samples before and after MDS progression showed that the mutations identified as last events (involving active signaling, myeloid transcription or tumor suppressor) seemed necessary for MDS development to be AML. Last mutations can exist at MDS diagnosis, or emerge at AML transformation, and involve a small group of genes. Single-allele CEBPA mutations and diverse TP53 mutations were checked as the most common last event mutations. Considering the necessity of last event mutations and limited gene involvement in AML transformations, it is possible to validate a small group of last events involved mutations to develop some new strategies to block MDS progression.
Single-step plasma-induced hierarchical structures for tunable water adhesion
Authors: Ko Tae-Jun , Park Sang Jin , Kim Min-Sung , Yoon Sun Mi , Kim Seong Jin , Oh Kyu Hwan , Nahm Sahn , Moon Myoung-Woon
Published: January 2020

Smart surfaces in nature have been extensively studied to identify their hierarchical structures in micro-/nanoscale to elucidate their superhydrophobicity with varying water adhesion. However, mimicking hybrid features in multiscale requires complex, multi-step processes. Here, we proposed a one-step process for the fabrication of hierarchical structures composed in micro-/nanoscales for superhydrophobic surfaces with tunable water adhesion. Hierarchical patterns were fabricated using a plasma-based selective etching process assisted by a dual scale etching mask. As the metallic mesh is placed above the substrate, it serves the role of dual scale etching masks on the substrate: microscale masks to form the micro-wall network and nanoscale masks to form high-aspect-ratio nanostructures. The micro-walls and nanostructures can be selectively hybridized by adjusting the gap distance between the mesh and the target surface: single nanostructures on a large area for a larger gap distance and hybrid/hierarchical structures with nanostructures nested on micro-walls for a shorter gap distance. The hierarchically nanostructured surface shows superhydrophobicity with low water adhesion, while the hybrid structured surface becomes become superhydrophobic with high adhesion. These water adhesion tunable surfaces were explored for water transport and evaporation. Additionally, we demonstrated a robust superhydrophobic surface with anti-reflectance over a large area.
Anisotropic conduction in the myocardium due to fibrosis: the effect of texture on wave propagation
Authors: Nezlobinsky T. , Solovyova O. , Panfilov A. V.
Published: January 2020

Cardiac fibrosis occurs in many forms of heart disease. It is well established that the spatial pattern of fibrosis, its texture, substantially affects the onset of arrhythmia. However, in most modelling studies fibrosis is represented by multiple randomly distributed short obstacles that mimic only one possible texture, diffuse fibrosis. An important characteristic feature of other fibrosis textures, such as interstitial and patchy textures, is that fibrotic inclusions have substantial length, which is suggested to have a pronounced effect on wave propagation. In this paper, we study the effect of the elongation of inexcitable inclusions (obstacles) on wave propagation in a 2D model of cardiac tissue described by the TP06 model for human ventricular cells. We study in detail how the elongation of obstacles affects various characteristics of the waves. We quantify the anisotropy induced by the textures, its dependency on the obstacle length and the effects of the texture on the shape of the propagating wave. Because such anisotropy is a result of zig-zag propagation we show, for the first time, quantification of the effects of geometry and source-sink relationship, on the zig-zag nature of the pathway of electrical conduction. We also study the effect of fibrosis in the case of pre-existing anisotropy and introduce a procedure for scaling of the fibrosis texture. We show that fibrosis can decrease or increase the preexisting anisotropy depending on its scaled texture.
Toward Reservoir-on-a-Chip: Rapid Performance Evaluation of Enhanced Oil Recovery Surfactants for Carbonate Reservoirs Using a Calcite-Coated Micromodel
Authors: Yun Wonjin , Chang Sehoon , Cogswell Daniel A. , Eichmann Shannon L. , Gizzatov Ayrat , Thomas Gawain , Al-Hazza Naimah , Abdel-Fattah Amr , Wang Wei
Published: January 2020

Enhanced oil recovery (EOR) plays a significant role in improving oil production. Tertiary EOR, including surfactant flooding, can potentially mobilize residual oil after water flooding. Prior to the field deployment, the surfactant performance must be evaluated using site-specific crude oil at reservoir conditions. Core flood experiments are common practice to evaluate surfactants for oil displacement efficiency using core samples. Core flood experiments, however, are expensive and time-consuming and do not allow for pore scale observations of fluid-fluid interactions. This work introduces the framework to evaluate the performance of EOR surfactants via a Reservoir-on-a-Chip approach, which uses microfluidic devices to mimic the oil reservoir. A unique feature of this study is the use of chemically modified micromodels such that the pore surfaces are representative of carbonate reservoir rock. To represent calcium carbonate reservoir pores, the inner channels of glass microfluidic devices were coated with thin layers of calcium carbonate nanocrystals and the surface was modified to exhibit oil-wet conditions through a crude oil aging process. During surfactant screening, oil and water phases were imaged by fluorescence microscopy to reveal the micro to macro scale mechanisms controlling surfactant-assisted oil recovery. The role of the interfacial tension (IFT) and wettability in the microfluidic device was simulated using a phase-field model and compared to laboratory results. We demonstrated the effect of low IFT at the oil-water interface and wettability alteration on surfactant-enhanced oil displacement efficiency; thus providing a time-efficient and low-cost strategy for quantitative and qualitative assessment. In addition, this framework is an effective method for pre-screening EOR surfactants for use in carbonate reservoirs prior to further core and field scale testing.
CRL4-Cereblon complex in Thalidomide Embryopathy: a translational investigation
Authors: Kowalski Thayne Woycinck , Gomes Julia do Amaral , Garcia Gabriela Barreto Caldas , Fraga Lucas Rosa , Paixao-Cortes Vanessa Rodrigues , Recamonde-Mendoza Mariana , Sanseverino Maria Teresa Vieira , Schuler-Faccini Lavinia , Vianna Fernanda Sales Luiz
Published: January 2020

The Cereblon-CRL4 complex has been studied predominantly with regards to thalidomide treatment of multiple myeloma. Nevertheless, the role of Cereblon-CRL4 in Thalidomide Embryopathy (TE) is still not understood. Not all embryos exposed to thalidomide develop TE, hence here we evaluate the role of the CRL4-Cereblon complex in TE variability and susceptibility. We sequenced CRBN, DDB1, CUL4A, IKZF1, and IKZF3 in individuals with TE. To better interpret the variants, we suggested a score and a heatmap comprising their regulatory effect. Differential gene expression after thalidomide exposure and conservation of the CRL4-Cereblon protein complex were accessed from public repositories. Results suggest a summation effect of Cereblon variants on pre-axial longitudinal limb anomalies, and heatmap scores identify the CUL4A variant rs138961957 as potentially having an effect on TE susceptibility. CRL4-Cereblon gene expression after thalidomide exposure and CLR4-Cereblon protein conservation does not explain the difference in Thalidomide sensitivity between species. In conclusion, we suggest that CRL4-Cereblon variants act through several regulatory mechanisms, which may influence CRL4-Cereblon complex assembly and its ability to bind thalidomide. Human genetic variability must be addressed not only to further understand the susceptibility to TE, but as a crucial element in therapeutics, including in the development of pharmacogenomics strategies.
Preventing traditional management can cause grassland loss within 30 years in southern Brazil
Authors: Sühs Rafael Barbizan , Giehl Eduardo Luís Hettwer , Peroni Nivaldo
Published: January 2020

Woody encroachment threatens several ecosystems around the world. In general, management of grasslands includes regulation of fire and grazing regimes. Changes in these two types of disturbances are potential drivers of woody encroachment. Here we assessed how the traditional management carried out by local landholders affects a highland grassland ecosystem in southern Brazil. We hypothesized that grasslands converted to protected areas undergo fast woody encroachment. To reconstruct changes in vegetation, we interviewed former and current landholders and coupled their knowledge with an analysis of aerial and satellite images. During the first 11 years without fire and cattle, woody encroachment in grasslands increased exponentially. Woody encroachment occurred mostly by the replacement of grasslands by shrublands. Meanwhile, grasslands under traditional management remained almost unchanged for the last 40 years. The management of fire by local landholders has been part of their traditional practices for decades. Such management prevents large-scale wildfires and maintains natural highland grasslands. The quick pace of shrub encroachment in such grasslands threatens its exclusive diversity, human well-being and regional cultural heritage. Thus, conservation policies are needed to regulate and instruct about the use of fire as a management tool in highland grasslands of southern Brazil.
Antiviral potential of 3′-sialyllactose- and 6′-sialyllactose-conjugated dendritic polymers against human and avian influenza viruses
Authors: Günther Sira Carolin , Maier Julian David , Vetter Janine , Podvalnyy Nikita , Khanzhin Nikolay , Hennet Thierry , Stertz Silke
Published: January 2020

Current treatment options for influenza virus infections in humans are limited and therefore the development of novel antivirals is of high priority. Inhibiting influenza virus attachment to host cells would provide an early and efficient block of the infection and thus, receptor analogs have been considered as options for antiviral treatment. Here, we describe the rapid and efficient synthesis of PAMAM dendrimers conjugated with either 3′-sialyllactose (3SL) or 6′-sialyllactose (6SL) and their potential to inhibit a diverse range of human and avian influenza virus strains. We show in a hemagglutination inhibition (HAI) assay that human IAV strains can be inhibited by (6SL)- and to a lesser extent also by (3SL)-conjugated PAMAM dendrimers. In contrast, avian strains could only be inhibited by (3SL)-conjugated dendrimers. Importantly, the differential sensitivities of human and avian IAV to the two types of sialyllactose-conjugated dendrimers could be confirmed in cell-based neutralization assays. Based on our findings, we suggest to further develop both, (3SL)- and (6SL)-conjugated PAMAM dendrimers, as influenza virus inhibitors.
Removal of Antibiotics from Water by Polymer of Intrinsic Microporosity: Isotherms, Kinetics, Thermodynamics, and Adsorption Mechanism
Authors: Alnajrani Mohammed N. , Alsager Omar A.
Published: January 2020

Traces of antibiotics within domestic and industrial effluents have toxic impact on human health as well as surrounding flora and fauna. Potential increase in antibiotic resistance of microorganisms is likely to rise due to the incomplete removal of antibiotics by traditional wastewater processing, methods such as membrane filtration and biological treatment. In this study, we investigated a novel class of material termed Polymer of Intrinsic Microporosity (PIM) that is based on amorphous microporous organic materials for the application of antibiotic removal form aqueous environments. The adsorption of four commonly used antibiotics (doxycycline, ciprofloxacin, penicillin G, and amoxicillin) was evaluated and found that at least 80% of the initial concentrations was eliminated under the optimized conditions. Langmuir and Freundlich models were then employed to correlate the equilibria data; the Freundlich model fit well the data in all cases. For kinetic data, pseudo-first and second order models were examined. Pseudo-second order model fit well the kinetic data and allowed the calculation of the adsorption rate constants. Thermodynamic parameters were obtained by conducting the adsorption studies at varied reaction temperatures. Surface potential, adsorption at various solution pHs, thermogravimetric analysis (TGA), Infrared spectroscopy (IR), and surface area experiments were conducted to draw possible adsorption mechanisms. The removal of antibiotics from water by PIM-1 is likely to be governed by both surface and pore-filling adsorption and could be facilitated by electrostatic interactions between the aromatic rings and charged functional groups as well as hydrogen bond formation between the adsorbent and adsorbate. Our work shows that the application of such novel microporous material could contribute to the removal of such challenging and persistent contaminants from wastewater with further optimizations of large-scale adsorption processes.