bluuebunny/crossref_metadata_2025 huggingface dataset:
MAJID FAKHRY, Al-Farabi, Founder of Islamic Neoplatonism: His Life, Works and Influence, Great Islamic Thinkers (Oxford: Oneworld, 2002). Pp. 176. $23.95
Authors: REISMAN DAVID
Published: January 2021

This is a fine, if somewhat simple, undergraduate introduction to the thought of Alfarabi—if you happen to be a student transported back to the late 1960s. There are a few entries in the bibliography dated after that, but these citations are mostly reprints of Alfarabi's published texts. Certainly, Fakhry's observations on Alfarabi's thought do not appear to have developed much beyond the scholarship of the late 1960s and early 1970s, and the reader justifiably might think that this is a publication of a rather old manuscript, dusted off and given a pleasant cover. Fakhry's efforts here remind one of the recent publication of Muhsin Mahdi's Alfarabi and the Foundation of Islamic Political Philosophy (Chicago, 2001) in that both are rather quaint products of an earlier time in the study of philosophy and science in Islam. It is difficult to say what has prompted this resurrection of mostly outdated scholarship, It may be a response on the part of publishers eager to get anything in print since the recent renewal of interest in things Islamic, though for all the wrong reasons.
Between Industry and Islam: Stonework and tomb construction in colonial-era India
Authors: LANZILLO AMANDA M.
Published: January 2021

In the late nineteenth and early twentieth centuries, monumental Muslim tombs in India served as spaces for refashioning local religious and social identities. Elite patrons, technical overseers, and stoneworkers engaged with new technologies of construction at sites meant to reflect claims on the Muslim past. This article interrogates divergent class understandings of monumental Muslim tombs in colonial-era India. It compares the construction of monumental Islamic tombs in the states of Hyderabad, Bhopal, and Rampur—three Muslim-led ‘native states’, quasi-autonomous polities under colonial oversight. By the late nineteenth century, many native state patrons employed a new middle class of technical intermediary to oversee tomb construction. The rise of this class created new hierarchies within construction, with apprenticeship-trained master craftsmen increasingly marginalized from state narratives and aligned with stoneworkers and other labourers. While patrons and middle-class intermediaries argued that new technologies and materials should be used to ‘modernize’ construction, they portrayed technical change as divorced from the religious symbolism of tombs. In contrast, workers integrated the religious and the technical, positioning technologies of construction within narratives of Muslim practice. The article uses native state tombs to analyse how labourers adapted to technical demands, without necessarily adopting state ideologies.
Does Student Loan Debt Structure Young People’s Housing Tenure? Evidence from England
Authors: DE GAYARDON ARIANE , CALLENDER CLAIRE , DESJARDINS STEPHEN L.
Published: January 2021

This article analyses the interaction between two policy areas affecting young people in England – housing and student funding. It is the first of its kind exploring a range of dynamics in the relationship between housing and student loan debt. Young people today are far less likely to own their home and are more likely to live with their parents than earlier generations. In parallel, higher education tuition fee increases have led to a growing share of students taking out loans and graduating with higher debt, which they will be repaying for most of their working lives. This research examines the relationship between student loans – having borrowed for higher education and attitudes towards debt – and housing tenure at age 25, using the Next Steps dataset. We find that young graduates who did not borrow for higher education are more likely to own their home and less likely to rent or live with their parents than graduates who borrowed for their studies or young people who never attended higher education. These results suggest that higher education funding policies and student loan debt play important roles in structuring young people’s housing in England.
Wrench Capabilities of a Kinematically Redundant Planar Parallel Manipulator
Authors: Boudreau Roger , Nokleby Scott , Gallant Marise
Published: January 2021

This paper presents a methodology to obtain the wrench capabilities of a kinematically redundant planar parallel manipulator using a wrench polytope approach. A methodology proposed by others for non-redundant and actuation-redundant manipulators is adapted to a kinematically redundant manipulator. Four wrench capabilities are examined: a pure force analysis, the maximum force for a prescribed moment, the maximum reachable force, and the maximum moment with a prescribed force. The proposed methodology, which finds the exact explicit solution for three of the four wrench capabilities, does not use optimization and is very efficient.
Branding in practice, or how an Amsterdam publisher used the city to promote Gerbrand Bredero (1585–1618)
Authors: Jansen Jeroen
Published: January 2021

This article explores how the publisher Cornelis vander Plasse managed to promote the literary career of the Dutch playwright Gerbrand Bredero (1585–1618) by using Amsterdam as a place. It is concerned with the way in which this Amsterdam-based publisher took decisions both to comply with Bredero's work and to derive maximum benefit from its publication. One of his strategies was to deploy the city as a recognizable trademark to Bredero's work. By using the advantages that the ‘place’ of Amsterdam offered him, he proved himself an expert in marketing and advertising, laying the foundation of Bredero's reputation as both an Amsterdam-based and national author in the centuries to follow.
“Islam” in Sanskrit doxography: a reconsideration via the writings of Madhusūdana Sarasvatī
Authors: NAIR SHANKAR
Published: January 2021

In the ongoing debate regarding the construction of the modern concept of “Hinduism”, recent research has considered the ways in which the pre-colonial encounter with Islam may have served as a catalyst in the crystallisation of an increasingly self-aware “Hindu” identity. Andrew Nicholson (Unifying Hinduism, 2010), in particular, has examined the genre of Sanskrit doxography to affirm that such a process of crystallisation was indeed taking place, as the transformations in this genre over time indicate a nascent Hindu identity emerging in the face of the “Muslim threat”. This article reevaluates Nicholson's account with reference to the writings of one Sanskrit intellectual operating at the height of Muslim power in South Asia: the figure of Madhusūdana Sarasvatī (fl. sixteenth-early seventeenth centuries). Madhusūdana's short doxography, the Prasthānabheda, often features in arguments for the pre-colonial roots of the concept of “Hinduism”; Madhusūdana's other doxographical writings, however, are typically neglected. Based upon an analysis of Madhusūdana's Siddhāntabindu and Vedāntakalpalatikā, this article suggests that a more nuanced consideration of the different audiences and authorial intentions that different doxographers had in mind can offer a modified picture of how early modern Sanskrit intellectuals were responding to the Muslim presence in the subcontinent.
Folic acid supplementation and risk for congenital hydrocephalus in China
Authors: Liu Jufen , Li Zhiwen , Ye Rongwei , Ren Aiguo , Liu Jianmeng
Published: January 2021

Objective:

We examined whether folic acid (FA) supplementation prevented congenital hydrocephalus (CH) in more than 200 000 births in China.

Design:

A large population-based cohort study.

Setting:

All births at 20 complete gestational weeks, including live births, stillbirths and pregnancy terminations, and all structural birth defects regardless of gestational week were recorded. The prevalence of births with CH was classified by maternal characteristics and FA supplementation. CH was diagnosed in accordance with code 742.3 of the International Classification of Diseases, Ninth Revision, Clinical Modification, while non-neural tube defect (NTD) CH refers to CH without anencephaly (740), spina bifida (741) or encephalocele (742·0).

Participants:

A total of 247 831 pregnant women who delivered with known outcomes were included.

Results:

A total of 206 cases of CH (0·83 per 1000 births) and 170 cases of non-NTD CH (0·69 per 1000 births) were recorded in the study. The prevalence of CH and non-NTD CH was higher in women in the no supplementation group than those in the FA supplementation group (0·92 and 0·72 v. 0·75 and 0·65 per 1000 births, respectively). FA supplementation during the periconceptional period significantly prevented CH (OR = 0·29, 95 % CI 0·12, 0·69) and non-NTD CH (OR = 0·34, 95 % CI 0·12, 0·97) in northern China, especially in a high-compliance group (≥ 80 %).

Conclusions:

Periconceptional FA supplementation did not significantly prevent CH overall in the current study. However, in the north of China with common maternal folate insufficiency, there was some evidence.
An application of PCA-DEA with the double-bootstrap approach to estimate the technical efficiency of New Zealand District Health Boards
Authors: Andrews Antony
Published: January 2021

Using yearly panel data from 2011 to 2017 on New Zealand District Health Boards (DHBs), this study combines principal component analysis and data envelopment intertemporal analysis with the double-bootstrap approach to estimate the technical efficiency of health care providers along with the trend of efficiency performances. The results show that although most large DHBs have improved their level of technical efficiency between 2011 and 2017, the majority of medium- and small-sized DHBs have not seen any noticeable improvement in their level of technical efficiency. The results also show that large and tertiary DHBs operate at a high level of technical efficiency. In contrast, most of the medium- and small-sized DHBs posted some of the lowest technical efficiency scores. Furthermore, the results show that medium- and small-sized DHBs have a higher average length of hospital stays which is found to be associated with decreasing levels of technical efficiency scores.
Precipitation‐Driven Pedogenic Weathering of Volcaniclastics on Early Mars
Authors: Ye B. , Michalski J. R.
Published: January 2021

Compositional stratigraphy, generally composed of Al‐rich clay minerals overlying Fe/Mg‐rich clay minerals, is observed in many locations on Mars. Here we describe the occurrence of such mineralogical stratigraphy in settings where the protoliths are almost certainly pyroclastic materials. One such example includes altered rocks high on the summit and flanks of explosive volcanoes in Thaumasia Planum. These clay‐bearing deposits are most consistent with precipitation‐driven weathering of ash deposits. Considering explosive volcanism was pervasive in the Noachian, the early sedimentary record of Mars in some locations is likely dominated by glassy, fragmented, porous, chemically reactive materials with highly specific surface area. These pyroclastic deposits were potentially a critical geological component linking clay minerals to elements of Mars’ climate, weathering, and sedimentary puzzle.
Time‐Series Prediction Approaches to Forecasting Deformation in Sentinel‐1 InSAR Data
Authors: Hill P. , Biggs J. , Ponce‐López V. , Bull D.
Published: January 2021

Time series of displacement are now routinely available from satellite InSAR and are used for flagging anomalous ground motion, but not yet forecasting. We test conventional time series forecasting methods such as SARIMA and supervised machine learning approaches such as long short‐term memory (LSTM) compared to simple function extrapolation. We focus initially on forecasting seasonal signals and begin by characterizing the time‐series using sinusoid fitting, seasonal decomposition, and autocorrelation functions. We find that the three measures are broadly comparable but identify different types of seasonal characteristic. We use this to select a set of 310 points with highly seasonal characteristics and test the three chosen forecasting methods over prediction windows of 1–9 months. The lowest overall median RMSE values are obtained for SARIMA when considering short term predictions (<1 month), whereas sinusoid extrapolation produces the lowest median RMSE values for longer predictions (>6 months). Machine learning methods (LSTM) perform less well. We then test the prediction methods on 2,000 randomly selected points with a range of seasonalities and find that simple extrapolation of a constant function performed better overall than any of the more sophisticated time series prediction methods. Comparisons between seasonality and RMSE show a small improvement in performance with increasing seasonality. This proof‐of‐concept study demonstrates the potential of time‐series prediction for InSAR data but also highlights the limitations of applying these techniques to nonperiodic signals or individual measurement points. We anticipate future developments, especially to shorter timescales, will have a broad range of potential applications, from infrastructure stability to volcanic eruptions.
High‐Resolution Simulations of Submesoscale Processes in the Baltic Sea: The Role of Storm Events
Authors: Chrysagi Evridiki , Umlauf Lars , Holtermann Peter , Klingbeil Knut , Burchard Hans
Published: January 2021

Recently discovered, ocean submesoscales have attracted considerable attention due to their ability to change the upper ocean stratification, affect vertical transport, and induce a downscale cascade of energy toward dissipation. In this paper, we highlight the effect of submesoscale fronts and filaments on surface layer properties and dynamics during storm events, extending previous idealized simulations toward real‐ocean applications. Here, we use the Baltic Sea as a natural laboratory to study the rich submesoscale activity of this system with the help of realistic high‐resolution numerical simulations. These simulations reveal a wealth of cold submesoscale filaments with sharp lateral buoyancy gradients, strong surface convergence, and high vertical velocities. Highly heterogeneous Mixed Layer Depth (MLD) modulations are associated with these features, maintaining locally reduced MLDs even during storm events due to vigorous submesoscale restratification. The interaction of near‐surface turbulence and submesoscale restratification results in strong and highly efficient mixing inside the submesoscale fronts. Focusing on a typical filament, it is shown that frontogenesis is associated with the convergent cross‐front circulation arising from a turbulent thermal wind balance, consistent with previous studies. We show that the sharp fronts generated by this process may become symmetrically unstable, and show enhanced (modeled) energy dissipation rates that are in good quantitative agreement with existing theoretical estimates.
Lagrangian Reconstruction to Extract Small‐Scale Salinity Variability From SMAP Observations
Authors: Barceló‐Llull Bàrbara , Drushka Kyla , Gaube Peter
Published: January 2021

As the resolution of observations and models improves, emerging evidence indicates that ocean variability on 1–200‐km scales is of fundamental importance to ocean circulation, air‐sea interaction, and biogeochemistry. In many regions, salinity variability dominates over thermal effects in forming density fronts. Unfortunately, current satellite observations of sea surface salinity (SSS) only resolve scales ≥40 km (or larger, depending on the product). In this study, we investigate small‐scale variability (≲25 km) by reconstructing gridded SSS observations made by the Soil Moisture Active Passive (SMAP) satellite in the northwest Atlantic Ocean. Using altimetric geostrophic currents, we numerically advect SMAP SSS fields to produce a Lagrangian reconstruction that represents small scales. Reconstructed fields are compared to in‐situ salinity observations made by a ship‐board thermosalinograph, revealing a marked improvement in small‐scale salinity variability when compared to the original SMAP fields, particularly from the continental shelf to the Gulf Stream. In the Sargasso Sea, however, both SMAP and the reconstructed fields contain higher variability than is observed in situ. Enhanced small‐scale salinity variability is concentrated in two bands: a northern band aligned with the continental shelfbreak and a southern band aligned with the Gulf Stream mean position. Seasonal differences in the small‐scale variability appear to covary with the seasonal cycle of the large‐scale SSS gradients resulting from the freshening of the coastal waters during periods of elevated river outflow.
Evolution of a Subducted Carbon‐Rich Filament on the Edge of the North Atlantic Gyre
Authors: Johnson Alexis R. , Omand Melissa M.
Published: January 2021

The oceanic biological carbon pump encompasses a variety of mechanisms by which CO2, fixed into organic form by phytoplankton, is transported from the sunlit surface layers to the interior ocean. Here, we investigate submesoscale and mixed layer subduction, estimated to represent ∼20% of global particulate organic carbon (POC) export. Seven Biogeochemical (BGC) Argo profiling floats were analyzed for evidence of subduction of POC in the North Atlantic Ocean, revealing a pattern in the seasonality. Although vertical processes that give rise to subduction are enhanced during late winter and spring, the bio‐optical evidence for intrusions—namely a deep local maxima in POC, co‐located with a temperature and salinity anomaly—were more commonly observed in the summer. We hypothesize that these deep intrusions can be long‐lived, having been subducted months earlier and persisting at depth throughout the warm season. We present a case study of a notable anomaly, observed in 10 consecutive BGC Argo profiles on the northeastern edge of the subtropical gyre. Analysis of the profiles, complemented by remote sensing and HYCOM model output, provides insight into the history and subsequent fate of the subducted water.
Microclimates in Fumarole Ice Caves on Volcanic Edifices—Mount Rainier, Washington, USA
Authors: Florea Lee J. , Pflitsch Andreas , Cartaya Eduardo , Stenner Christian
Published: January 2021

The fumarole ice caves of Mount Rainier in the Cascade Volcanic Arc in Washington, USA, provide unique insight into the dynamic equilibrium between thermal flux of fumaroles on volcanic edifices and snow accumulation on summit glaciers. More than 3.5 km of surveyed cave passage nearly circumnavigate the East Crater, reaching within 19 m of the 4,392 m summit and extending to 144 m depth along the glacier‐crater boundary. The large circum‐crater passage connects entrances on the crater rim to steep transverse passages, and cave morphology is maintained by fumarole gas convection and advection. A melt‐ and condensate‐formed lake, Lake Adélie, occupies a portion of the circum‐crater passage. Hourly data were collected between August 2016 and August 2017 and included the measured temperatures at three fumaroles, the cave air temperature and pressure, the lake water temperature and depth, and the outside temperature and snow depth at Paradise Visitors Center. Time‐series analyses of these data reveal complex associations between synoptic to seasonal weather, fumarole activity, and lake level. On seasonal and longer scales, fumarole temperatures follow independent pathways connected to spatial and temporal changes in volcanic heat flux and the circulation of glacial melt. Major snowfall seals the cave entrances, increasing cave air temperature and pressure from fumarole output and causing rising lake levels from increased melt until entrances reopen. Repeating freeze‐thaw cycles observed in the cave monitoring data are a primary cause of crater mass wasting. Despite these transient variations, the scale and morphology of the caves is preserved over decadal or longer scales.
Androgen receptor gain in circulating free DNA and splicing variant 7 in exosomes predict clinical outcome in CRPC patients treated with abiraterone and enzalutamide
Authors: Del Re M. , Conteduca V. , Crucitta S. , Gurioli G. , Casadei C. , Restante G. , Schepisi G. , Lolli C. , Cucchiara F. , Danesi R. , De Giorgi U.
Published: January 2021

Background

Androgen receptor (AR) signaling inhibitors represent the standard treatment in metastatic castration resistance prostate cancer (mCRPC) patients. However, some patients display a primary resistance, and several studies investigated the role of the AR as a predictive biomarker of response to treatment. This study is aimed to evaluate the role of AR in liquid biopsy to predict clinical outcome to AR signaling inhibitors in mCRPC patients.

Methods

Six milliliters of plasma samples were collected before first-line treatment with abiraterone or enzalutamide. Circulating free DNA (cfDNA) and exosome-RNA were isolated for analysis of AR gain and AR splice variant 7 (AR-V7), respectively, by digital droplet PCR.

Results

Eighty-four mCRPC patients received abiraterone (n = 40) or enzalutamide (n = 44) as first-line therapy. Twelve patients (14.3%) presented AR gain and 30 (35.7%) AR-V7+ at baseline. Median progression-free survival (PFS) and overall survival (OS) were significantly longer in AR-V7− vs AR-V7+ patients (24.3 vs 5.4 months, p < 0.0001; not reached vs 16.2 months, p = 0.0001, respectively). Patients carrying the AR gain had a median PFS of 4.8 vs 24.3 months for AR normal patients (p < 0.0001). Median OS was significantly longer in AR normal vs patients with AR gain (not reached vs 8.17 months, p < 0.0001). A significant correlation between AR-V7 and AR gain was observed (r = 0.28; p = 0.01). The AR gain/AR-V7 combined analysis confirmed a strong predictive effect for biomarkers combination vs patients without any AR aberration (PFS 3.8 vs 28 month, respectively; OS 6.1 vs not reached, respectively; p < 0.0001).

Conclusions

The present study demonstrates that cfDNA and exosome-RNA are both a reliable source of AR variants and their combined detection in liquid biopsy predicts resistance to AR signaling inhibitors.
Serum d-serine levels are altered in early phases of Alzheimer’s disease: towards a precocious biomarker
Authors: Piubelli Luciano , Pollegioni Loredano , Rabattoni Valentina , Mauri Marco , Princiotta Cariddi Lucia , Versino Maurizio , Sacchi Silvia
Published: January 2021

d-Serine acts as a co-agonist of N-methyl-d-aspartate receptors (NMDAR) which appear overactivated in AD, while d-aspartate is a modulatory molecule acting on NMDAR as a second agonist. The aim of this work is to clarify whether the levels of these d-amino acids in serum are deregulated in AD, with the final goal to identify novel and precocious biomarkers in AD. Serum levels of l- and d-enantiomers of serine and aspartate were determined by HPLC using a pre-column derivatization procedure and a selective enzymatic degradation. Experimental data obtained from age-matched healthy subjects (HS) and AD patients were statistically evaluated by considering age, gender, and disease progression, and compared. Minor changes were apparent in the serum l- and d-aspartate levels in AD patients compared to HS. A positive correlation for the d-serine level and age was apparent in the AD cohort. Notably, the serum d-serine level and the d-/total serine ratio significantly increased with the progression of the disease. Gender seems to have a minor effect on the levels of all analytes tested. This work proposes that the serum d-serine level and d-/total serine ratio values as novel and valuable biomarkers for the progression of AD: the latter parameter allows to discriminate CDR 2 and CDR 1 patients from healthy (CDR 0) individuals.
Mild behavioral impairment and its relation to tau pathology in preclinical Alzheimer’s disease
Authors: Johansson Maurits , Stomrud Erik , Insel Philip S. , Leuzy Antoine , Johansson Per Mårten , Smith Ruben , Ismail Zahinoor , Janelidze Shorena , Palmqvist Sebastian , van Westen Danielle , Mattsson-Carlgren Niklas , Hansson Oskar
Published: January 2021

Mild behavioral impairment (MBI) is suggested as risk marker for neurodegenerative diseases, such as Alzheimer’s disease (AD). Recently, pathologic tau deposition in the brain has been shown closely related to clinical manifestations, such as cognitive deficits. Yet, associations between tau pathology and MBI have rarely been investigated. It is further debated if MBI precedes cognitive deficits in AD. Here, we explored potential mechanisms by which MBI is related to AD, this by studying associations between MBI and tau in preclinical AD. In all, 50 amyloid-β-positive cognitively unimpaired subjects (part of the BioFINDER-2 study) underwent MBI-checklist (MBI-C) to assess MBI, and the Alzheimer’s Disease Assessment Scale – Cognitive subscale (ADAS-Cog) delayed word recall (ADAS-DR) to assess episodic memory. Early tau pathology was determined using tau-PET ([18F]RO948 retention in entorhinal cortex/hippocampus) and cerebrospinal fluid (CSF) P-tau181. Regression models were used to test for associations. We found that higher tau-PET signal in the entorhinal cortex/hippocampus and CSF P-tau181 levels were associated with higher MBI-C scores (β = 0.010, SE = 0.003, p = 0.003 and β = 1.263, SE = 0.446, p = 0.007, respectively). When MBI-C and ADAS-DR were entered together in the regression models, tau-PET (β = 0.009, p = 0.009) and CSF P-tau181 (β = 0.408, p = 0.006) were predicted by MBI-C, but not ADAS-DR. We conclude that in preclinical AD, MBI is associated with tau independently from memory deficits. This denotes MBI as an important early clinical manifestation related to tau pathology in AD.
Metabolic regulation of telomere silencing by SESAME complex-catalyzed H3T11 phosphorylation
Authors: Zhang Shihao , Yu Xilan , Zhang Yuan , Xue Xiangyan , Yu Qi , Zha Zitong , Gogol Madelaine , Workman Jerry L. , Li Shanshan
Published: January 2021

Telomeres are organized into a heterochromatin structure and maintenance of silent heterochromatin is required for chromosome stability. How telomere heterochromatin is dynamically regulated in response to stimuli remains unknown. Pyruvate kinase Pyk1 forms a complex named SESAME (Serine-responsive SAM-containing Metabolic Enzyme complex) to regulate gene expression by phosphorylating histone H3T11 (H3pT11). Here, we identify a function of SESAME in regulating telomere heterochromatin structure. SESAME phosphorylates H3T11 at telomeres, which maintains SIR (silent information regulator) complex occupancy at telomeres and protects Sir2 from degradation by autophagy. Moreover, SESAME-catalyzed H3pT11 directly represses autophagy-related gene expression to further prevent autophagy-mediated Sir2 degradation. By promoting H3pT11, serine increases Sir2 protein levels and enhances telomere silencing. Loss of H3pT11 leads to reduced Sir2 and compromised telomere silencing during chronological aging. Together, our study provides insights into dynamic regulation of silent heterochromatin by histone modifications and autophagy in response to cell metabolism and aging.
Topological features without a lattice in Rashba spin-orbit coupled atoms
Authors: Valdés-Curiel A. , Trypogeorgos D. , Liang Q.-Y. , Anderson R. P. , Spielman I. B.
Published: January 2021

Topological order can be found in a wide range of physical systems, from crystalline solids, photonic meta-materials and even atmospheric waves to optomechanic, acoustic and atomic systems. Topological systems are a robust foundation for creating quantized channels for transporting electrical current, light, and atmospheric disturbances. These topological effects are quantified in terms of integer-valued ‘invariants’, such as the Chern number, applicable to the quantum Hall effect, or the $${{\mathbb{Z}}}_{2}$$

Z

2

invariant suitable for topological insulators. Here, we report the engineering of Rashba spin-orbit coupling for a cold atomic gas giving non-trivial topology, without the underlying crystalline structure that conventionally yields integer Chern numbers. We validated our procedure by spectroscopically measuring both branches of the Rashba dispersion relation which touch at a single Dirac point. We then measured the quantum geometry underlying the dispersion relation using matter-wave interferometry to implement a form of quantum state tomography, giving a Berry’s phase with magnitude π. This implies that opening a gap at the Dirac point would give two dispersions (bands) each with half-integer Chern number, potentially implying new forms of topological transport.
Asymmetrizing an icosahedral virus capsid by hierarchical assembly of subunits with designed asymmetry
Authors: Zhao Zhongchao , Wang Joseph Che-Yen , Zhang Mi , Lyktey Nicholas A. , Jarrold Martin F. , Jacobson Stephen C. , Zlotnick Adam
Published: January 2021

Symmetrical protein complexes are ubiquitous in biology. Many have been re-engineered for chemical and medical applications. Viral capsids and their assembly are frequent platforms for these investigations. A means to create asymmetric capsids may expand applications. Here, starting with homodimeric Hepatitis B Virus capsid protein, we develop a heterodimer, design a hierarchical assembly pathway, and produce asymmetric capsids. In the heterodimer, the two halves have different growth potentials and assemble into hexamers. These preformed hexamers can nucleate co-assembly with other dimers, leading to Janus-like capsids with a small discrete hexamer patch. We can remove the patch specifically and observe asymmetric holey capsids by cryo-EM reconstruction. The resulting hole in the surface can be refilled with fluorescently labeled dimers to regenerate an intact capsid. In this study, we show how an asymmetric subunit can be used to generate an asymmetric particle, creating the potential for a capsid with different surface chemistries.
Strong geometry dependence of the Casimir force between interpenetrated rectangular gratings
Authors: Wang Mingkang , Tang L. , Ng C. Y. , Messina Riccardo , Guizal Brahim , Crosse J. A. , Antezza Mauro , Chan C. T. , Chan H. B.
Published: January 2021

Quantum fluctuations give rise to Casimir forces between two parallel conducting plates, the magnitude of which increases monotonically as the separation decreases. By introducing nanoscale gratings to the surfaces, recent advances have opened opportunities for controlling the Casimir force in complex geometries. Here, we measure the Casimir force between two rectangular silicon gratings. Using an on-chip detection platform, we achieve accurate alignment between the two gratings so that they interpenetrate as the separation is reduced. Just before interpenetration occurs, the measured Casimir force is found to have a geometry dependence that is much stronger than previous experiments, with deviations from the proximity force approximation reaching a factor of ~500. After the gratings interpenetrate each other, the Casimir force becomes non-zero and independent of displacement. This work shows that the presence of gratings can strongly modify the Casimir force to control the interaction between nanomechanical components.
A non-invasive multimodal foetal ECG–Doppler dataset for antenatal cardiology research
Authors: Sulas Eleonora , Urru Monica , Tumbarello Roberto , Raffo Luigi , Sameni Reza , Pani Danilo
Published: January 2021

Non-invasive foetal electrocardiography (fECG) continues to be an open topic for research. The development of standard algorithms for the extraction of the fECG from the maternal electrophysiological interference is limited by the lack of publicly available reference datasets that could be used to benchmark different algorithms while providing a ground truth for foetal heart activity when an invasive scalp lead is unavailable. In this work, we present the Non-Invasive Multimodal Foetal ECG-Doppler Dataset for Antenatal Cardiology Research (NInFEA), the first open-access multimodal early-pregnancy dataset in the field that features simultaneous non-invasive electrophysiological recordings and foetal pulsed-wave Doppler (PWD). The dataset is mainly conceived for researchers working on fECG signal processing algorithms. The dataset includes 60 entries from 39 pregnant women, between the 21st and 27th week of gestation. Each dataset entry comprises 27 electrophysiological channels (2048 Hz, 22 bits), a maternal respiration signal, synchronised foetal trans-abdominal PWD and clinical annotations provided by expert clinicians during signal acquisition. MATLAB snippets for data processing are also provided.
High-pH reversed-phase fractionated neural retina proteome of normal growing C57BL/6 mouse
Authors: Sze Ying Hon , Zhao Qian , Cheung Jimmy Ka Wai , Li King Kit , Tse Dennis Yan Yin , To Chi Ho , Lam Thomas Chuen
Published: January 2021

The retina is a key sensory tissue composed of multiple layers of cell populations that work coherently to process and decode visual information. Mass spectrometry-based proteomics approach has allowed high-throughput, untargeted protein identification, demonstrating the presence of these proteins in the retina and their involvement in biological signalling cascades. The comprehensive wild-type mouse retina proteome was prepared using a novel sample preparation approach, the suspension trapping (S-Trap) filter, and further fractionated with high-pH reversed phase chromatography involving a total of 28 injections. This data-dependent acquisition (DDA) approach using a Sciex TripleTOF 6600 mass spectrometer identified a total of 7,122 unique proteins (1% FDR), and generated a spectral library of 5,950 proteins in the normal C57BL/6 mouse retina. Data-independent acquisition (DIA) approach relies on a large and high-quality spectral library to analyse chromatograms, this spectral library would enable access to SWATH-MS acquisition to provide unbiased, multiplexed, and quantification of proteins in the mouse retina, acting as the most extensive reference library to investigate retinal diseases using the C57BL/6 mouse model.
Next-generation sequencing for identification of actionable gene mutations in intestinal-type sinonasal adenocarcinoma
Authors: Sánchez-Fernández Paula , Riobello Cristina , Costales María , Vivanco Blanca , Cabal Virginia N. , García-Marín Rocío , Suárez-Fernández Laura , López Fernando , Cabanillas Rubén , Hermsen Mario A. , Llorente José Luis
Published: January 2021

Intestinal-type sinonasal adenocarcinoma (ITAC) is a rare tumor carrying poor prognosis and needing new treatment options. The aim of this study was to identify actionable gene mutations that can guide new personalized target-specific therapies in ITAC patients. A series of 48 tumor and 27 corresponding germline DNA samples were analyzed by next generation sequencing using a panel of 120 genes. In total, 223 sequence variants were found in 70 genes. Matched tumor/germline comparison in 27 cases revealed that 57% were in fact germline variants. In 20 of these 27 cases, 58 somatic variants in 33 different genes were identified, the most frequent being PIK3CA (5 cases), APC and ATM (4 cases), and KRAS, NF1, LRP1B and BRCA1 (3 cases). Many of the somatic gene variants affected PI3K, MAPK/ERK, WNT and DNA repair signaling pathways, although not in a mutually exclusive manner. None of the alterations were related to histological ITAC subtype, tumor stage or survival. Our data showed that thorough interpretation of somatic mutations requires sequencing analysis of the corresponding germline DNA. Potentially actionable somatic mutations were found in 20 of 27 cases, 8 of which being biomarkers of FDA-approved targeted therapies. Our data implicate new possibilities for personalized treatment of ITAC patients.
Impact of PET data driven respiratory motion correction and BSREM reconstruction of 68Ga-DOTATATE PET/CT for differentiating neuroendocrine tumors (NET) and intrapancreatic accessory spleens (IPAS)
Authors: Liberini Virginia , Kotasidis Fotis , Treyer Valerie , Messerli Michael , Orita Erika , Engel-Bicik Ivette , Siebenhüner Alexander , Huellner Martin W.
Published: January 2021

To evaluate whether quantitative PET parameters of motion-corrected 68Ga-DOTATATE PET/CT can differentiate between intrapancreatic accessory spleens (IPAS) and pancreatic neuroendocrine tumor (pNET). A total of 498 consecutive patients with neuroendocrine tumors (NET) who underwent 68Ga-DOTATATE PET/CT between March 2017 and July 2019 were retrospectively analyzed. Subjects with accessory spleens (n = 43, thereof 7 IPAS) and pNET (n = 9) were included, resulting in a total of 45 scans. PET images were reconstructed using ordered-subsets expectation maximization (OSEM) and a fully convergent iterative image reconstruction algorithm with β-values of 1000 (BSREM1000). A data-driven gating (DDG) technique (MOTIONFREE, GE Healthcare) was applied to extract respiratory triggers and use them for PET motion correction within both reconstructions. PET parameters among different samples were compared using non-parametric tests. Receiver operating characteristics (ROC) analyzed the ability of PET parameters to differentiate IPAS and pNETs. SUVmax was able to distinguish pNET from accessory spleens and IPAs in BSREM1000 reconstructions (p < 0.05). This result was more reliable using DDG-based motion correction (p < 0.003) and was achieved in both OSEM and BSREM1000 reconstructions. For differentiating accessory spleens and pNETs with specificity 100%, the ROC analysis yielded an AUC of 0.742 (sensitivity 56%)/0.765 (sensitivity 56%)/0.846 (sensitivity 62%)/0.840 (sensitivity 63%) for SUVmax 36.7/41.9/36.9/41.7 in OSEM/BSREM1000/OSEM + DDG/BSREM1000 + DDG, respectively. BSREM1000 + DDG can accurately differentiate pNET from accessory spleen. Both BSREM1000 and DDG lead to a significant SUV increase compared to OSEM and non-motion-corrected data.
Higher-order structure of polymer melt described by persistent homology
Authors: Shimizu Yohei , Kurokawa Takanori , Arai Hirokazu , Washizu Hitoshi
Published: January 2021

The optimal method of the polymer Materials Informatics (MI) has not been developed because the amorphous nature of the higher-order structure affects these properties. We have now tried to develop the polymer MI’s descriptor of the higher-order structure using persistent homology as the topological method. We have experimentally studied the influence of the MD simulation cell size as the higher-order structure of the polymer on its electrical properties important for a soft material sensor or actuator device. The all-atom MD simulation of the polymer has been calculated and the obtained atomic coordinate has been analyzed by the persistent homology. The change in the higher-order structure by different cell size simulations affects the dielectric constant, although these changes are not described by a radial distribution function (RDF). On the other hand, using the 2nd order persistent diagram (PD), it was found that when the cell size is small, the island-shaped distribution become smoother as the cell size increased. There is the same tendency for the condition of change in the monomer ratio, the polymer chain length or temperature. As a result, the persistent homology may express the higher-order structure generated by the MD simulation as a descriptor of the polymer MI.
Simultaneous mapping of EMCD signals and crystal orientations in a transmission electron microscope
Authors: Ali Hasan , Rusz Jan , Warnatz Tobias , Hjörvarsson Björgvin , Leifer Klaus
Published: January 2021

When magnetic properties are analysed in a transmission electron microscope using the technique of electron magnetic circular dichroism (EMCD), one of the critical parameters is the sample orientation. Since small orientation changes can have a strong impact on the measurement of the EMCD signal and such measurements need two separate measurements of conjugate EELS spectra, it is experimentally non-trivial to measure the EMCD signal as a function of sample orientation. Here, we have developed a methodology to simultaneously map the quantitative EMCD signals and the local orientation of the crystal. We analyse, both experimentally and by simulations, how the measured magnetic signals evolve with a change in the crystal tilt. Based on this analysis, we establish an accurate relationship between the crystal orientations and the EMCD signals. Our results demonstrate that a small variation in crystal tilt can significantly alter the strength of the EMCD signal. From an optimisation of the crystal orientation, we obtain quantitative EMCD measurements.
Heterosexual, gay, and lesbian people’s reactivity to virtual caresses on their embodied avatars’ taboo zones
Authors: Fusaro Martina , Lisi Matteo P. , Tieri Gaetano , Aglioti Salvatore Maria
Published: January 2021

Embodying an artificial agent through immersive virtual reality (IVR) may lead to feeling vicariously somatosensory stimuli on one’s body which are in fact never delivered. To explore whether vicarious touch in IVR reflects the basic individual and social features of real-life interpersonal interactions we tested heterosexual men/women and gay men/lesbian women reacting subjectively and physiologically to the observation of a gender-matched virtual body being touched on intimate taboo zones (like genitalia) by male and female avatars. All participants rated as most erogenous caresses on their embodied avatar taboo zones. Crucially, heterosexual men/women and gay men/lesbian women rated as most erogenous taboo touches delivered by their opposite and same gender avatar, respectively. Skin conductance was maximal when taboo touches were delivered by female avatars. Our study shows that IVR may trigger realistic experiences and ultimately allow the direct exploration of sensitive societal and individual issues that can otherwise be explored only through imagination.
Formulation, optimization and characterization of allantoin-loaded chitosan nanoparticles to alleviate ethanol-induced gastric ulcer: in-vitro and in-vivo studies
Authors: Aman Reham Mokhtar , Zaghloul Randa A. , El-Dahhan Marwa S.
Published: January 2021

Allantoin (ALL) is a phytochemical possessing an impressive array of biological activities. Nonetheless, developing a nanostructured delivery system targeted to augment the gastric antiulcerogenic activity of ALL has not been so far investigated. Consequently, in this survey, ALL-loaded chitosan/sodium tripolyphosphate nanoparticles (ALL-loaded CS/STPP NPs) were prepared by ionotropic gelation technique and thoroughly characterized. A full 24factorial design was adopted using four independently controlled parameters (ICPs). Comprehensive characterization, in vitro evaluations as well as antiulcerogenic activity study against ethanol-induced gastric ulcer in rats of the optimized NPs formula were conducted. The optimized NPs formula, (CS (1.5% w/v), STPP (0.3% w/v), CS:STPP volume ratio (5:1), ALL amount (13 mg)), was the most convenient one with drug content of 6.26 mg, drug entrapment efficiency % of 48.12%, particle size of 508.3 nm, polydispersity index 0.29 and ζ-potential of + 35.70 mV. It displayed a sustained in vitro release profile and mucoadhesive strength of 45.55%. ALL-loaded CS/STPP NPs (F-9) provoked remarkable antiulcerogenic activity against ethanol-induced gastric ulceration in rats, which was accentuated by histopathological, immunohistochemical (IHC) and biochemical studies. In conclusion, the prepared ALL-loaded CS/STPP NPs could be presented to the phytomedicine field as an auspicious oral delivery system for gastric ulceration management.
Color-tunable bioluminescence imaging portfolio for cell imaging
Authors: Tamaki Shota , Kitada Nobuo , Kiyama Masahiro , Fujii Rika , Hirano Takashi , Kim Sung Bae , Maki Shojiro
Published: January 2021

The present study describes a color-tunable imaging portfolio together with twelve novel coelenterazine (CTZ) analogues. The three groups of CTZ analogues create diverse hues of bioluminescence (BL) ranging from blue to far red with marine luciferases. We found that the hue completes the whole color palette in the visible region and shows red-shifted BL with a marine luciferase: for example, Renilla luciferase 8 (RLuc8) and Artificial Luciferase 16 (ALuc16) show 187 nm- and 105 nm-redshifted spectra, respectively, by simply replacing the substrate CTZ with 1d. The optical properties of the new CTZ analogues were investigated such as the kinetic parameters, dose dependency, and luciferase specificity. The 2-series CTZ analogues interestingly have specificity to ALucs and are completely dark with RLuc derivatives, and 3d is highly specific to only NanoLuc. We further determined the theoretical background of the red-shifted BL maximum wavelengths (λBL) values according to the extended π conjugation of the CTZ backbone using Density Functional Theory (DFT) calculations. This color-tunable BL imaging system provides a useful multicolor imaging portfolio that efficiently images molecular events in mammalian cells.
Corals regulate the distribution and abundance of Symbiodiniaceae and biomolecules in response to changing water depth and sea surface temperature
Authors: Sivaguru Mayandi , Todorov Lauren G. , Miller Carly A. H. , Fouke Courtney E. , Munro Cara M. O. , Fouke Kyle W. , Fouke Kaitlyn E. , Baughman Melinda E. , Fouke Bruce W.
Published: January 2021

The Scleractinian corals Orbicella annularis and O. faveolata have survived by acclimatizing to environmental changes in water depth and sea surface temperature (SST). However, the complex physiological mechanisms by which this is achieved remain only partially understood, limiting the accurate prediction of coral response to future climate change. This study quantitatively tracks spatial and temporal changes in Symbiodiniaceae and biomolecule (chromatophores, calmodulin, carbonic anhydrase and mucus) abundance that are essential to the processes of acclimatization and biomineralization. Decalcified tissues from intact healthy Orbicella biopsies, collected across water depths and seasonal SST changes on Curaçao, were analyzed with novel autofluorescence and immunofluorescence histology techniques that included the use of custom antibodies. O. annularis at 5 m water depth exhibited decreased Symbiodiniaceae and increased chromatophore abundances, while O. faveolata at 12 m water depth exhibited inverse relationships. Analysis of seasonal acclimatization of the O. faveolata holobiont in this study, combined with previous reports, suggests that biomolecules are differentially modulated during transition from cooler to warmer SST. Warmer SST was also accompanied by decreased mucus production and decreased Symbiodiniaceae abundance, which is compensated by increased photosynthetic activity enhanced calcification. These interacting processes have facilitated the remarkable resiliency of the corals through geological time.