bluuebunny/crossref_metadata_2025 huggingface dataset:
Wall reabsorption effects on heat and mass transfer of viscous fluid in a narrow leaky tube
Authors: Shahzad Aamir , Khan Waqar A.
Published: January 2021

The steady heat and mass transfer problem of flow of an incompressible Newtonian fluid is investigated in this study. The axisymmetric flow of a non-isothermal and highly viscous fluid is considered through a narrow leaky tube of uniform cross-section with linear reabsorption across the wall. The Navier–Stokes equations are solved for axially symmetric and slow flow in the tube. The effects of linear reabsorption parameter on the dimensionless radial and axial velocities, temperature, concentration, shear stress, leakage flux, fractional reabsorption, pressure drop across the tube as well as the Nusselt and Sherwood numbers have been investigated analytically. For 50% fractional reabsorption, inlet radial velocity is half of the reabsorption velocity along the tube. It has been shown that increase in the strength of linear reabsorption parameter considerably reduces the radial velocity, while, axial velocity shows opposite behaviour. At the exit region ($$z=0.9$$

z
=
0.9

), reverse flow phenomenon is observed for higher values of reabsorption parameter. The pressure, flow rate and wall shear stress decreases after entrance region ($$z=0.1$$

z
=
0.1

) of the tube. Nusselt number and Sherwood number show opposite behaviour inside the tube. At $$z=0.1$$

z
=
0.1

the magnitude of Nusselt number is maximum, while the Sherwood number is minimum at the exit region with higher value of reabsorption parameter.
Food forensics on gelatine source via ultra-high-performance liquid chromatography diode-array detector and principal component analysis
Authors: Ismail Azilawati Mohd , Sani Muhamad Shirwan Abdullah , Azid Azman , Zaki Nor Nadiha Mohd , Arshad Syariena , Tukiran Nur Azira , Abidin Siti Aimi Sarah Zainal , Samsudin Mohd Saiful , Ismail Amin
Published: January 2021

This study provided a step-by-step procedure to investigate the distribution of 17 amino acids (AAs) in 50 fish, 50 bovine and 54 porcine gelatines using Ultra-High-Performance Liquid Chromatography Diode-Array Detector (UHPLC–DAD) with the incorporation of principal component analysis (PCA). Dataset pre-processing step, including outlier removal, analysis of variance (ANOVA), dataset adequacy test, dataset transformation and correlation test was performed before the PCA. The method rendered linearity range of 37.5–1000 pmol/µL and accuracy of 85–111% recovery. The bovine and porcine gelatines showed a similar ranking while the l-Alanine (Ala), l-Arginine (Arg) and l-Glutamic acid (Glu) concentrations had differed the fish gelatine from the bovine and porcine gelatines. The PCA, which explained 77.013% cumulative variability at eigenvalue of 5.436, showed AAs with strong FL in PC1 had polar and nonpolar side chains while AAs with strong FL in PC2 had polar side chain. The AAs with moderate and weak FL in PC1 had a nonpolar side chain. The AAs with strong FL of in PC1 were also the same AAs with 7, 6 and 5 strong CMs as determined in the correlation test. The second PCA showed that the l-Serine (Ser), Arg, Glycine (Gly), l-Threonine (Thr), l-Methionine (Met), l-Histidine (His) and L-Hydroxyproline (Hyp) were significant in fish gelatine; Hyp, Met, Thr, Ser, His, Gly, and Arg in bovine gelatine; and l-Proline (Pro), l-Tyrosine (Tyr), l-Valine (Val), l-Leucine (Leu), and l-Phenylalanine (Phe) in porcine gelatine. The 100% fish, bovine and porcine gelatines accommodated grouping 1, 2 and 3, respectively, which proved that AAs with strong FL (Hyp, His, Ser, Arg, Gly, Thr, Pro, Tyr, Met, Val, Leu and Phe) were the significant AAs and becomes the biomarkers to identify the gelatine source. From this study, the PCA was a useful tool to analyse a multivariate dataset that could provide an in-depth understanding of AA distributions as compared to ANOVA and correlation test.
Study of critical failure surface influencing factors for loose rock slope
Authors: Wang Shuhong , Ahmed Zulkifl , Wang Pengyu
Published: January 2021

In current research, a novel geometrical technique is introduced to estimate the length (L) of sliding arc by considering slip surface entry point distance (de). Morgenstern-Price limiting equilibrium and strength reduction methods are selected within the framework of SLOPE/W and FLAC3D softwares respectively, to study the sliding mechanism and stability-effecting factor for a loose rock slope comprise of two different material. Also, the variability influence of strength parameters (cohesion force and friction angle) and the depth of pore water pressure on safety factor, failure depth (D) and distribution range of critical failure surface (CFS) are investigated through software. The results show that the shear strength parameters and the depth of pore water pressure plays a significant role in altering overall stability and the distribution range of CFS for a loose rock slope. Shallow failure with composite failure surface is much easier to occur for loose rock slope subjected to pore water pressure and material heterogeneity. These findings can be effectively used for loose rock slope reinforcement design.
Creating Immersive Virtual Environments Based on Open Geospatial Data and Game Engines
Authors: Keil Julian , Edler Dennis , Schmitt Thomas , Dickmann Frank
Published: January 2021

Modern game engines like Unity allow users to create realistic 3D environments containing terrains as well as natural and artificial objects easily and swiftly. In addition, recent advances of game engine capabilities enable effortless implementation of virtual reality (VR) compatibility. 3D environments created with VR compatibility can be experienced from an egocentric and stereoscopic perspective that surpasses the immersion of the ‘classical’ screen-based perception of 3D environments. Not only game developers benefit from the possibilities provided by game engines. The ability to use geospatial data to shape virtual 3D environments opens a multitude of possibilities for geographic applications, such as construction planning, spatial hazard simulations or representation of historical places. The multi-perspective, multimodal reconstruction of three-dimensional space based on game engine technology today supports the possibility of linking different approaches of geographic work more closely. Free geospatial data that can be used for spatial reconstructions is provided by numerous national and regional official institutions. However, the file format of these data sources is not standardized and game engines only support a limited number of file formats. Therefore, format transformation is usually required to apply geospatial data to virtual 3D environments. This paper presents several workflows to apply digital elevation data and 3D city model data from OpenStreetMap and the Open.NRW initiative to Unity-based 3D environments. Advantages and disadvantages of different sources of geospatial data are discussed. In addition, implementation of VR compatibility is described. Finally, benefits of immersive VR implementation and characteristics of current VR hardware are discussed in the context of specific geographic application scenarios.
Correction to: From indoor exposure to inhaled particle deposition: A multiphase journey of inhaled particles
Authors: Inthavong Kiao
Published: January 2021

The article “From indoor exposure to inhaled particle deposition: A multiphase journey of inhaled particles” written by Kiao Inthavong, was originally published electronically on the publisher’s internet portal (currently SpringerLink) on 22 October 2019 without open access. After publication in Volume 2, Issue 2, page 59–78, the author(s) decided to opt for Open Choice and to make the article an open access publication. Therefore, the copyright of the article has been changed to © The Author(s) 2020 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Rapid shortening of survival duration in early fatal cases of COVID-19, Wuhan, China
Authors: Zhang Yuzhou , Bambrick Hilary , Tong Shilu , Lambert Stephen B , Hu Wenbiao
Published: January 2021

Severe COVID-19 cases place immediate pressure on hospital resources. To assess this, we analysed survival duration in the first 39 fatal cases in Wuhan, China. Time from onset and hospitalization to death declined rapidly, from ~40 to 7 days, and ~25 to 4 days, respectively, in the outbreak’s first month.
Subglottic suction frequency and adverse ventilator-associated events during critical illness
Authors: Abdallah Hatem O. , Weingart Melanie F. , Fuller Risa , Pegues David , Fitzpatrick Rebecca , Kelly Brendan J.
Published: January 2021

Objective:

Tracheal intubation and mechanical ventilation provide essential support for patients with respiratory failure, but the course of mechanical ventilation may be complicated by adverse ventilator-associated events (VAEs), which may or may not be associated with infection. We sought to understand how the frequency of subglottic suction, an indicator of the quantity of sputum produced by ventilated patients, relates to the onset of all VAEs and infection-associated VAEs.

Design:

We performed a case-crossover study including 87 patients with VAEs, and we evaluated 848 days in the pre-VAE period at risk for a VAE.

Setting and participants:

Critically ill patients were recruited from the medical intensive care unit of an academic medical center.

Methods:

We used the number of as-needed subglottic suctioning events performed per calendar day to quantify sputum production, and we compared the immediate pre-VAE period to the preceding period. We used CDC surveillance definitions for VAE and to categorize whether events were infection associated or not.

Results:

Sputum quantity measured by subglottic suction frequency is greater in the period immediately prior to VAE than in the preceding period. However, it does not discriminate well between infection-associated VAEs and VAEs without associated infection.

Conclusions:

Subglottic suction frequency may serve as a valuable marker of sputum quantity, and it is associated with risk of a VAE. However, our results require validation in a broader population of mechanically ventilated patients and intensive care settings.
Insights into the shockwave attenuation in miniature shock tubes
Authors: Janardhanraj S. , Abhishek K. , Jagadeesh G.
Published: January 2021

Miniature shock tubes are finding growing importance in a variety of interdisciplinary applications. There is a lack of experimental data to validate the existing shock tube flow models that explain the shockwave attenuation in pressure-driven miniature shock tubes. This paper gives insights into the shock formation and shock propagation phenomena in miniature shock tubes of 2, 6 and 10 mm square cross-sections operated at diaphragm rupture pressure ratios in the range 5–25 and driven section initially at ambient conditions. Pressure measurements and visualization studies are carried out in a new miniature table-top shock tube system using nitrogen and helium as driver gases. The experimental findings are validated using a shock tube model explained in terms of two regions: (i) the shock formation region, dominated by wave interactions due to the diaphragm's finite rupture time; and (ii) the shock propagation region, where the shockwave attenuation occurs mainly due to wall effects and boundary layer growth. Correlations to predict the variation of shock Mach number in the shock formation region and shock propagation region work well for the present findings and experimental data reported in the literature. Similar flow features are observed in the shock tubes at the same dimensionless time stamps. The formation of the planar shock front scales proportionally with the diameter of the shock tube. The peak Mach number attained by the shockwave is higher as the shock tube diameter increases.
LIFSCHITZ REALIZABILITY AS A TOPOLOGICAL CONSTRUCTION
Authors: RATHJEN MICHAEL , SWAN ANDREW W.
Published: January 2021

We develop a number of variants of Lifschitz realizability for $\mathbf {CZF}$ by building topological models internally in certain realizability models. We use this to show some interesting metamathematical results about constructive set theory with variants of the lesser limited principle of omniscience including consistency with unique Church’s thesis, consistency with some Brouwerian principles and variants of the numerical existence property.
Universal Suffrage as Decolonization
Authors: DUONG KEVIN
Published: January 2021

This essay reconstructs an important but forgotten dream of twentieth-century political thought: universal suffrage as decolonization. The dream emerged from efforts by Black Atlantic radicals to conscript universal suffrage into wider movements for racial self-expression and cultural revolution. Its proponents believed a mass franchise could enunciate the voice of colonial peoples inside imperial institutions and transform the global order. Recuperating this insurrectionary conception of the ballot reveals how radicals plotted universal suffrage and decolonization as a single historical process. It also places decolonization’s fate in a surprising light: it may have been the century’s greatest act of disenfranchisement. As dependent territories became nation-states, they lost their voice in metropolitan assemblies whose affairs affected them long after independence.
GENERALISED WEIGHTED COMPOSITION OPERATORS ON BERGMAN SPACES INDUCED BY DOUBLING WEIGHTS
Authors: LIU BIN
Published: January 2021

We characterise bounded and compact generalised weighted composition operators acting from the weighted Bergman space$A^p_\omega $, where$0<p<\infty $and$\omega $belongs to the class$\mathcal {D}$of radial weights satisfying a two-sided doubling condition, to a Lebesgue space$L^q_\nu $. On the way, we establish a new embedding theorem on weighted Bergman spaces$A^p_\omega $which generalises the well-known characterisation of the boundedness of the differentiation operator$D^n(f)=f^{(n)}$from the classical weighted Bergman space$A^p_\alpha $to the Lebesgue space$L^q_\mu $, induced by a positive Borel measure$\mu $, to the setting of doubling weights.
The relationship between inflammatory dietary pattern and incidence of periodontitis
Authors: Alhassani Ahmed A. , Hu Frank B. , Rosner Bernard A. , Tabung Fred K. , Willett Walter C. , Joshipura Kaumudi J.
Published: January 2021

The long-term inflammatory impact of diet could potentially elevate the risk of periodontal disease through modification of systemic inflammation. The aim of the present study was to prospectively investigate the associations between a food-based, reduced rank regression (RRR)-derived, empirical dietary inflammatory pattern (EDIP) and incidence of periodontitis. The study population was composed of 34 940 men from the Health Professionals Follow-Up Study, who were free of periodontal disease and major illnesses at baseline (1986). Participants provided medical and dental history through mailed questionnaires every 2 years and dietary data through validated semi-quantitative FFQ every 4 years. We used Cox proportional hazard models to examine the associations between EDIP scores and validated self-reported incidence of periodontal disease over a 24-year follow-up period. No overall association between EDIP and the risk of periodontitis was observed; the hazard ratio comparing the highest EDIP quintile (most proinflammatory diet) with the lowest quintile was 0·99 (95 % CI 0·89, 1·10, P-value for trend = 0·97). A secondary analysis showed that among obese non-smokers (i.e. never and former smokers at baseline), the hazard ratio for periodontitis comparing the highest EDIP quintile with the lowest was 1·39 (95 % CI 0·98, 1·96, P-value for trend = 0·03). In conclusion, no overall association was detected between EDIP and incidence of self-reported periodontitis in the study population. From the subgroups evaluated, EDIP was significantly associated with increased risk of periodontitis only among non-smokers who were obese. Hence, this association must be interpreted with caution.
IDENTIFYING THE JUS COGENS NORM IN THE JUS AD BELLUM
Authors: Johnston Katie A
Published: January 2021

This article argues that if there is a jus cogens norm in the jus ad bellum, it must be the customary norm which prohibits non-consensual uses of force that are neither validly authorised under the UN Charter nor lawful exercises of self-defence. In doing so this article will clarify the method by which jus cogens norms should be identified, based on a correct understanding and application of what it means for a norm to be ‘accepted and recognized as a norm from which no derogation is permitted’. It is argued that all existing jus cogens norms must be norms of customary law, and that the uncertainty regarding the scope of the jus cogens norm prohibiting force results from uncertainty as to the structure of the underlying customary and treaty law norms in the jus ad bellum.
Design and Implementation of a Cable Inspection Robot for Cable-Stayed Bridges
Authors: Wang Zhipeng , He Bin , Zhou Yanmin , Liu Ke , Zhang Chenghong
Published: January 2021

Cable is the most important bearing structure of the cable-stayed bridges. Its safety has been of crucial public concern. Traditional manual cable inspection method has many defects such as low inspection efficiency, poor reliability and hazardous working environment. In this paper, a new wirelessly controlled cable-climbing robot enabling safe and convenient inspection of stay cables is proposed. The designed robot is composed of two modules, joined by four turnbuckles to form a closed structure that clasps the cable. The robot is controlled wirelessly by a ground-based station, and a DC power is supplied via an onboard lithium battery. The climbing principle and mechanical structure of this robot are introduced. The static model of the robot during obstacle negotiation is established. The relationships of the driving force and resistance with obstacle height to determine the obstacle-negotiation capability of the robot are obtained. The effects of cable diameter, cable inclination and preload force on obstacle climbing ability of the robot are also analyzed. The experiments verify that the robot could climb random inclined cables and overcome an obstacle of 2.42 mm in height with a mass of 5 kg payload.
The length of an s-increasing sequence of r-tuples
Authors: Gowers W. T. , Long J.
Published: January 2021

We prove a number of results related to a problem of Po-Shen Loh [9], which is equivalent to a problem in Ramsey theory. Let a = (a1, a2, a3) and b = (b1, b2, b3) be two triples of integers. Define a to be 2-less than b if ai < bi for at least two values of i, and define a sequence a1, …, am of triples to be 2-increasing if ar is 2-less than as whenever r < s. Loh asks how long a 2-increasing sequence can be if all the triples take values in {1, 2, …, n}, and gives a log* improvement over the trivial upper bound of n2 by using the triangle removal lemma. In the other direction, a simple construction gives a lower bound of n3/2. We look at this problem and a collection of generalizations, improving some of the known bounds, pointing out connections to other well-known problems in extremal combinatorics, and asking a number of further questions.
His Fate Was Larger than Himself: Andrei D. Sakharov’s Centenary
Authors: Hargittai István
Published: January 2021

The world-renowned physicist Andrei D. Sakharov (1921–1989) was ‘the father of the Soviet hydrogen bomb’ and, as such, an architect of the Soviet superpower. He developed into a fierce fighter for human rights, distinguished by the Nobel Peace Prize. In his words, ‘my fate was larger than what would have followed from my personality. I was merely trying to be worthy of my fate.’1 His life and career provide thought-provoking lessons and is worthy of review on the eve of his centennial.
Growth and long-run sustainability
Authors: Cairns Robert D. , Martinet Vincent
Published: January 2021

From any state of economic and environmental assets, the maximin value defines the highest level of utility that can be sustained forever. Along any development path, the maximin value evolves over time according to investment decisions. If the current level of utility is lower than this value, there is room for growth of both the utility level and the maximin value. For any resource allocation mechanism (ram) and economic dynamics, growth is limited by the long-run level of the maximin value, which is an endogenous dynamic sustainability constraint. If utility reaches this limit, sustainability imposes growth to stop, and the adoption of maximin decisions instead of the currentram. We illustrate this pattern in two canonical models, the simple fishery and a two-sector economy with a nonrenewable resource. We discuss what our results imply for the assessment of sustainability in the short and the long run in non-optimal economies.
A SUGGESTION FOR A DYNAMIC MULTIFACTOR MODEL (DMFM)
Authors: Gibson Heather D. , Hall Stephen G. , Tavlas George S.
Published: January 2021

We provide a new way of deriving a number of dynamic unobserved factors from a set of variables. We show how standard principal components may be expressed in state space form and estimated using the Kalman filter. To illustrate our procedure, we perform two exercises. First, we use it to estimate a measure of the current account imbalances among northern and southern euro area countries that developed during the period leading up to the outbreak of the euro area crisis, before looking at adjustment in the post-crisis period. Second, we show how these dynamic factors can improve forecasting of the euro exchange rate.
“TIME-RELEASE” OUTPUT RESPONSES TO PUBLIC EDUCATION EXPENDITURES
Authors: Atems Bebonchu , Blankenau William
Published: January 2021

This paper argues that output can respond to public education spending in a delayed and persistent manner through human capital accumulation. We refer to this as a “time-release” response, reflecting that the output response grows as students exposed to increased expenditures sequentially enter the labor market. We first develop and calibrate a stochastic overlapping generations model to formalize the propagation of spending shocks over a long time horizon. We then empirically explore this time-release aspect of shocks to government education expenditures on output using US state-level data for the period 1963–2016 and a panel structural vector autoregression methodology. Consistent with the model, our empirical results show that the dynamic response of output to shocks to government education expenditures is positive, significant, and long-lasting.
EB1 Is Essential for Spindle Formation and Chromosome Alignment During Oocyte Meiotic Maturation in Mice
Authors: Zhou Dongjie , Nie Zheng-Wen , Cui Xiang-Shun
Published: January 2021

The cytoskeleton plays an orchestrating role in polarized cell growth. Microtubules (MTs) not only play critical roles in chromosome alignment and segregation but also control cell shape, division, and motility. A member of the plus-end tracking proteins, end-binding protein 1 (EB1), regulates MT dynamics and plays vital roles in maintaining spindle symmetry and chromosome alignment during mitosis. However, the role of EB1 in mouse oocyte meiosis remains unknown. Here, we examined the localization patterns and expression levels of EB1 at different stages. EB1 protein level was found to be stable during meiosis. EB1 mainly localized along the spindle and had a similar localization pattern as that of α-tubulin. The EB1 protein was degraded with a Trim-Away method, and the results were further confirmed with western blotting and immunofluorescence. At 12 h of culture after EB1 knockdown (KD), a reduced number of mature MII oocytes were observed. EB1 KD led to spindle disorganization, chromosome misalignment, and missegregation; β-catenin protein binds to actin via the adherens junctional complex, which was significantly reduced in the EB1 KD oocytes. Collectively, we propose that the impairment of EB1 function manipulates spindle formation, thereby promoting chromosomal loss, which is expected to fuel aneuploidy and possibly fertilization failure.
Global Anglican Discourse and Women’s Ordination in Kenya: The Controversy in Kirinyaga, 1979–1992, and its Legacy
Authors: Kapinde Stephen Asol , Higgs Eleanor Tiplady
Published: January 2021

In the 1980s, the question of women’s ordination in the Anglican Church of Kenya (ACK) caused a controversy in Kirinyaga diocese, in which Archbishop David Gitari (1937–2013) played a critical role as an advocate for women. This controversy is just one example of how African Christian women have faced multiple material and theological obstacles to ordination, both in the Anglican Church and in other churches. Through an analysis of institutional texts we show how the issue of women’s ordination has been addressed in formal Anglican decision-making processes. We also outline the patriarchal attitudes that characterized the wider discourse of women’s ordination in Kenya and in the Anglican Communion, and discuss how this discourse informed Gitari’s intervention. Opposition to women’s ordination is only one facet of sexism in the ACK, as was implicitly recognized by Gitari in his wider project of ‘holistic development’.
Somatic Symptom Disorder, Conversion Disorder, and Chronic Pain: Pediatric Clinician Perspectives
Authors: Edwards Kim R. , McMurtry C. Meghan , Dick Bruce , Lewinson Rebecca , Dhariwal Amrit , Katz Joel
Published: January 2021

Objectives: The appropriateness and relevance of somatic symptom disorder and conversion disorder ( American Psychiatric Association, 2013 ) diagnoses are in question as they relate to pediatric chronic pain. This survey-based study on pediatric chronic pain explores how these psychiatric diagnoses are made and perceived and how treatment of patients is approached by Canadian health care professionals working in pediatric chronic pain clinics. Method: Health care professionals ( N = 50) completed the survey, which contained both qualitative and quantitative items. Results: Of participants, 88% reported moderate/advanced training in pain, whereas only 26% reported moderate/advanced training in somatic symptom disorder and conversion disorder. Somatic symptom disorder and conversion disorder were reportedly diagnosed in approximately 17% and 5% of young people with chronic pain, respectively; however, overall, the participants were not confident or only slightly confident when diagnosing these disorders. There were no major differences in the reported interventions used to treat pain, somatic symptom disorder, or conversion disorder. Conclusions: These results highlight the need for standardized training in pain and psychiatric assessment, diagnosis, and treatment; diagnostic guidelines; and how to best provide this training to health care staff who work with young people with chronic pain.

Implications for Impact Statement

These results raise questions about the conceptualization of chronic pain, somatic symptom disorder, and conversion disorder, and point to the need for further research, improved training, clearer differential diagnostic criteria, and effective treatments.
The Role of Pediatric Psychologists in Mitigating Disability-Specific Barriers Among Youth During the COVID-19 Pandemic
Authors: Lund Emily M. , Gabrielli Joy
Published: January 2021

Objective: The objective of this article is to provide information about the ways in which the COVID-19 pandemic may affect the physical and psychosocial well-being of youth with disabilities, including assessment and intervention considerations for pediatric psychologists and other mental health professionals. Methods: This article reviews the emerging literature on the impact of the COVID-19 pandemic on children and adolescents and connects it to the unique needs of youth with disabilities and their families. Results: The COVID-19 pandemic magnifies the inequalities and barriers faced by youth with disabilities and creates new difficulties in accessing health, education, and other intervention services. In particular, this article discusses how the pandemic has affected (a) access to special education; (b) access to health care and personal care; and (c) mental health, including exposures to traumatic events. Conclusions: The COVID-19 pandemic has the potential to greatly affect the biopsychosocial well-being of youth with disabilities. Pediatric psychologists can play an active role in mitigating these effects at both the individual and system levels.

Implications for Impact Statement

This article addresses the unique and increased barriers faced by youth with disabilities and their families during the COVID-19 pandemic (e.g., access to education and health care, trauma and mental health concerns) and how pediatric psychologists can help them during these difficult times with effective, culturally responsive, and evidence-based strategies.
Ensemble learning of diffractive optical networks
Authors: Rahman Md Sadman Sakib , Li Jingxi , Mengu Deniz , Rivenson Yair , Ozcan Aydogan
Published: January 2021

A plethora of research advances have emerged in the fields of optics and photonics that benefit from harnessing the power of machine learning. Specifically, there has been a revival of interest in optical computing hardware due to its potential advantages for machine learning tasks in terms of parallelization, power efficiency and computation speed. Diffractive deep neural networks (D2NNs) form such an optical computing framework that benefits from deep learning-based design of successive diffractive layers to all-optically process information as the input light diffracts through these passive layers. D2NNs have demonstrated success in various tasks, including object classification, the spectral encoding of information, optical pulse shaping and imaging. Here, we substantially improve the inference performance of diffractive optical networks using feature engineering and ensemble learning. After independently training 1252 D2NNs that were diversely engineered with a variety of passive input filters, we applied a pruning algorithm to select an optimized ensemble of D2NNs that collectively improved the image classification accuracy. Through this pruning, we numerically demonstrated that ensembles of N = 14 and N = 30 D2NNs achieve blind testing accuracies of 61.14 ± 0.23% and 62.13 ± 0.05%, respectively, on the classification of CIFAR-10 test images, providing an inference improvement of >16% compared to the average performance of the individual D2NNs within each ensemble. These results constitute the highest inference accuracies achieved to date by any diffractive optical neural network design on the same dataset and might provide a significant leap to extend the application space of diffractive optical image classification and machine vision systems.
Constrained proteome allocation affects coexistence in models of competitive microbial communities
Authors: Pacciani-Mori Leonardo , Suweis Samir , Maritan Amos , Giometto Andrea
Published: January 2021

Microbial communities are ubiquitous and play crucial roles in many natural processes. Despite their importance for the environment, industry and human health, there are still many aspects of microbial community dynamics that we do not understand quantitatively. Recent experiments have shown that the structure and composition of microbial communities are intertwined with the metabolism of the species that inhabit them, suggesting that properties at the intracellular level such as the allocation of cellular proteomic resources must be taken into account when describing microbial communities with a population dynamics approach. In this work, we reconsider one of the theoretical frameworks most commonly used to model population dynamics in competitive ecosystems, MacArthur’s consumer-resource model, in light of experimental evidence showing how proteome allocation affects microbial growth. This new framework allows us to describe community dynamics at an intermediate level of complexity between classical consumer-resource models and biochemical models of microbial metabolism, accounting for temporally-varying proteome allocation subject to constraints on growth and protein synthesis in the presence of multiple resources, while preserving analytical insight into the dynamics of the system. We first show with a simple experiment that proteome allocation needs to be accounted for to properly understand the dynamics of even the simplest microbial community, i.e. two bacterial strains competing for one common resource. Then, we study our consumer-proteome-resource model analytically and numerically to determine the conditions that allow multiple species to coexist in systems with arbitrary numbers of species and resources.
Plasma glial fibrillary acidic protein is elevated in cognitively normal older adults at risk of Alzheimer’s disease
Authors: Chatterjee Pratishtha , Pedrini Steve , Stoops Erik , Goozee Kathryn , Villemagne Victor L. , Asih Prita R. , Verberk Inge M. W. , Dave Preeti , Taddei Kevin , Sohrabi Hamid R. , Zetterberg Henrik , Blennow Kaj , Teunissen Charlotte E. , Vanderstichele Hugo M. , Martins Ralph N.
Published: January 2021

Glial fibrillary acidic protein (GFAP), an astrocytic cytoskeletal protein, can be measured in blood samples, and has been associated with Alzheimer’s disease (AD). However, plasma GFAP has not been investigated in cognitively normal older adults at risk of AD, based on brain amyloid-β (Aβ) load. Cross-sectional analyses were carried out for plasma GFAP and plasma Aβ1–42/Aβ1–40 ratio, a blood-based marker associated with brain Aβ load, in participants (65–90 years) categorised into low (Aβ−,n = 63) and high (Aβ+,n = 33) brain Aβ load groups via Aβ positron emission tomography. Plasma GFAP, Aβ1–42, and Aβ1–40 were measured using the Single molecule array (Simoa) platform. Plasma GFAP levels were significantly higher (p < 0.00001), and plasma Aβ1–42/Aβ1–40 ratios were significantly lower (p < 0.005), in Aβ+ participants compared to Aβ− participants, adjusted for covariates age, sex, and apolipoprotein E-ε4 carriage. A receiver operating characteristic curve based on a logistic regression of the same covariates, the base model, distinguished Aβ+ from Aβ− (area under the curve, AUC = 0.78), but was outperformed when plasma GFAP was added to the base model (AUC = 0.91) and further improved with plasma Aβ1–42/Aβ1–40 ratio (AUC = 0.92). The current findings demonstrate that plasma GFAP levels are elevated in cognitively normal older adults at risk of AD. These observations suggest that astrocytic damage or activation begins from the pre-symptomatic stage of AD and is associated with brain Aβ load. Observations from the present study highlight the potential of plasma GFAP to contribute to a diagnostic blood biomarker panel (along with plasma Aβ1–42/Aβ1–40 ratios) for cognitively normal older adults at risk of AD.
Metabolic features of recurrent major depressive disorder in remission, and the risk of future recurrence
Authors: Mocking Roel J. T. , Naviaux Jane C. , Li Kefeng , Wang Lin , Monk Jonathan M. , Bright A. Taylor , Figueroa Caroline A. , Schene Aart H. , Ruhé Henricus G. , Assies Johanna , Naviaux Robert K.
Published: January 2021

Recurrent major depressive disorder (rMDD) is a relapsing-remitting disease with high morbidity and a 5-year risk of recurrence of up to 80%. This was a prospective pilot study to examine the potential diagnostic and prognostic value of targeted plasma metabolomics in the care of patients with rMDD in remission. We used an established LC-MS/MS platform to measure 399 metabolites in 68 subjects with rMDD (n = 45 females and 23 males) in antidepressant-free remission and 59 age- and sex-matched controls (n = 40 females and 19 males). Patients were then followed prospectively for 2.5 years. Metabolomics explained up to 43% of the phenotypic variance. The strongest biomarkers were gender specific. 80% of the metabolic predictors of recurrence in both males and females belonged to 6 pathways: (1) phospholipids, (2) sphingomyelins, (3) glycosphingolipids, (4) eicosanoids, (5) microbiome, and (6) purines. These changes traced to altered mitochondrial regulation of cellular redox, signaling, energy, and lipid metabolism. Metabolomics identified a chemical endophenotype that could be used to stratify rrMDD patients at greatest risk for recurrence with an accuracy over 0.90 (95%CI = 0.69–1.0). Power calculations suggest that a validation study of at least 198 females and 198 males (99 cases and 99 controls each) will be needed to confirm these results. Although a small study, these results are the first to show the potential utility of metabolomics in assisting with the important clinical challenge of prospectively identifying the patients at greatest risk of recurrence of a depressive episode and those who are at lower risk.
Venetoclax induces deep hematologic remissions in t(11;14) relapsed/refractory AL amyloidosis
Authors: Premkumar Vikram J. , Lentzsch Suzanne , Pan Samuel , Bhutani Divaya , Richter Joshua , Jagannath Sundar , Liedtke Michaela , Jaccard Arnaud , Wechalekar Ashutosh D. , Comenzo Raymond , Sanchorawala Vaishali , Royer Bruno , Rosenzweig Michael , Valent Jason , Schönland Stefan , Fonseca Rafael , Wong Sandy , Kapoor Prashant
Published: January 2021

Venetoclax is efficacious in relapsed/refractory t(11;14) multiple myeloma, thus warranting investigation in light-chain amyloidosis (AL). This retrospective cohort includes 43 patients with previously treated AL, from 14 centers in the US and Europe. Thirty-one patients harbored t(11;14), 11 did not, and one t(11;14) status was unknown. Patients received a venetoclax-containing regimen for at least one 21- or 28-day cycle; the median prior treatments was three. The hematologic response rate for all patients was 68%; 63% achieved VGPR/CR. t(11;14) patients had higher hematologic response (81% vs. 40%) and higher VGPR/CR rate (78% vs. 30%, odds ratio: 0.12, 95% CI 0.02–0.62) than non-t(11;14) patients. For the unsegregated cohort, median progression-free survival (PFS) was 31.0 months and median OS was not reached (NR). For t(11;14), median PFS was NR and for non-t(11;14) median PFS was 6.7 months (HR: 0.14, 95% CI 0.04–0.53). Multivariate analysis incorporating age, sex, prior lines of therapy, and disease stage suggested a risk reduction for progression or death in t(11;14) patients. Median OS was NR for either subgroup. The organ response rate was 38%; most responders harbored t(11;14). Grade 3 or higher adverse events occurred in 19% with 7% due to infections. These promising results require confirmation in a randomized clinical trial.
The role of E3 ubiquitin ligases in the development and progression of glioblastoma
Authors: Humphreys Luke M. , Smith Paul , Chen Zhuoyao , Fouad Shahd , D’Angiolella Vincenzo
Published: January 2021

Despite recent advances in our understanding of the disease, glioblastoma (GB) continues to have limited treatment options and carries a dismal prognosis for patients. Efforts to stratify this heterogeneous malignancy using molecular classifiers identified frequent alterations in targetable proteins belonging to several pathways including the receptor tyrosine kinase (RTK) and mitogen-activated protein kinase (MAPK) signalling pathways. However, these findings have failed to improve clinical outcomes for patients. In almost all cases, GB becomes refractory to standard-of-care therapy, and recent evidence suggests that disease recurrence may be associated with a subpopulation of cells known as glioma stem cells (GSCs). Therefore, there remains a significant unmet need for novel therapeutic strategies. E3 ubiquitin ligases are a family of >700 proteins that conjugate ubiquitin to target proteins, resulting in an array of cellular responses, including DNA repair, pro-survival signalling and protein degradation. Ubiquitin modifications on target proteins are diverse, ranging from mono-ubiquitination through to the formation of polyubiquitin chains and mixed chains. The specificity in substrate tagging and chain elongation is dictated by E3 ubiquitin ligases, which have essential regulatory roles in multiple aspects of brain cancer pathogenesis. In this review, we begin by briefly summarising the histological and molecular classification of GB. We comprehensively describe the roles of E3 ubiquitin ligases in RTK and MAPK, as well as other, commonly altered, oncogenic and tumour suppressive signalling pathways in GB. We also describe the role of E3 ligases in maintaining glioma stem cell populations and their function in promoting resistance to ionizing radiation (IR) and chemotherapy. Finally, we consider how our knowledge of E3 ligase biology may be used for future therapeutic interventions in GB, including the use of blood–brain barrier permeable proteolysis targeting chimeras (PROTACs).
BUB1B promotes extrahepatic cholangiocarcinoma progression via JNK/c-Jun pathways
Authors: Jiao Chen Yu , Feng Qin Chao , Li Chang Xian , Wang Dong , Han Sheng , Zhang Yao Dong , Jiang Wang Jie , Chang Jiang , Wang Xuehao , Li Xiang Cheng
Published: January 2021

Currently, the controversy regarding the expression profile and function of BUB1B in different malignancies still exist. In this project, we aimed to explore the role and molecular mechanism of BUB1B in the progression of extrahepatic cholangiocarcinoma (ECC). The expression levels of BUB1B in human ECC were evaluated by immunohistochemistry, western blot, and real-time PCR. The role and mechanism of BUB1B in CCA cell proliferation and invasion were investigated in both in vitro and in vivo functional studies. To indicate the clinical significance, a tissue microarray was performed on 113 ECC patients, followed by univariate and multivariate analyses. The expression of BUB1B was increased in both human CCA tissues and CCA cells. Results from loss-of-function and gain-of-function experiments suggested that the inhibition of BUB1B decreased the proliferation and invasiveness of CCA cells in vitro and in vivo, while overexpression of BUB1B achieved the opposite effect. Furthermore, the activation of c-Jun N-terminal kinase-c-Jun (JNK)-c-Jun pathway was regulated by BUB1B. BUB1B regulated the proliferation and invasiveness of CAA cells in a JNK-c-Jun-dependent manner. Clinically, ECC patients with BUB1B high expression had worse overall survival and recurrence-free survival than those with BUB1B low expression. Multivariate analysis identified that BUB1B was an independent predictor for postoperative recurrence and overall survival of ECC patients. In conclusion, BUB1B promoted ECC progression via JNK/c-Jun pathways. These findings suggested that BUB1B could be a potential therapeutic target and a biomarker for predicting prognosis for ECC patients.
ALKBH5 suppresses tumor progression via an m6A-dependent epigenetic silencing of pre-miR-181b-1/YAP signaling axis in osteosarcoma
Authors: Yuan Ye , Yan Gege , He Mingyu , Lei Hong , Li Linqiang , Wang Yang , He Xiaoqi , Li Guanghui , Wang Quan , Gao Yuelin , Qu Zhezhe , Mei Zhongting , Shen Zhihua , Pu Jiaying , Wang Ao , Zhao Wei , Jiang Huiwei , Du Weijie , Yang Lei
Published: January 2021

ALKBH5 is the main enzyme for m6A-based demethylation of RNAs and it has been implicated in many biological and pathophysiological processes. Here, we aimed to explore the potential involvement of ALKBH5 in osteosarcoma and decipher the underlying cellular/molecular mechanisms. We discovered downregulated levels of demethylase ALKBH5 were correlated with increased m6A methylation in osteosarcoma cells/tissues compared with normal osteoblasts cells/tissues. ALKBH5 overexpression significantly suppressed osteosarcoma cell growth, migration, invasion, and trigged cell apoptosis. In contrast, inhibition of ALKBH5 produced the opposite effects. Whereas ALKBH5 silence enhanced m6A methylations of pre-miR-181b-1 and YAP-mRNA exerting oncogenic functions in osteosarcoma. Moreover, upregulation of YAP or downregulation of mature miR-181b-5p displayed a remarkable attenuation of anti-tumor activities caused by ALKBH5. Further results revealed that m6A methylated pre-miR-181b-1 was subsequently recognized by m6A-binding protein YTHDF2 to mediate RNA degradation. However, methylated YAP transcripts were recognized by YTHDF1 to promote its translation. Therefore, ALKBH5-based m6A demethylation suppressed osteosarcoma cancer progression through m6A-based direct/indirect regulation of YAP. Thus, ALKBH5 overexpression might be considered a new approach of replacement therapy for osteosarcoma treatment.
A map of copy number variations in the Tunisian population: a valuable tool for medical genomics in North Africa
Authors: Romdhane Lilia , Mezzi Nessrine , Dallali Hamza , Messaoud Olfa , Shan Jingxuan , Fakhro Khalid A. , Kefi Rym , Chouchane Lotfi , Abdelhak Sonia
Published: January 2021

Copy number variation (CNV) is considered as the most frequent type of structural variation in the human genome. Some CNVs can act on human phenotype diversity, encompassing rare Mendelian diseases and genomic disorders. The North African populations remain underrepresented in public genetic databases in terms of single-nucleotide variants as well as for larger genomic mutations. In this study, we present the first CNV map for a North African population using the Affymetrix Genome-Wide SNP (single-nucleotide polymorphism) array 6.0 array genotyping intensity data to call CNVs in 102 Tunisian healthy individuals. Two softwares, PennCNV and Birdsuite, were used to call CNVs in order to provide reliable data. Subsequent bioinformatic analyses were performed to explore their features and patterns. The CNV map of the Tunisian population includes 1083 CNVs spanning 61.443 Mb of the genome. The CNV length ranged from 1.017 kb to 2.074 Mb with an average of 56.734 kb. Deletions represent 57.43% of the identified CNVs, while duplications and the mixed loci are less represented. One hundred and three genes disrupted by CNVs are reported to cause 155 Mendelian diseases/phenotypes. Drug response genes were also reported to be affected by CNVs. Data on genes overlapped by deletions and duplications segments and the sequence properties in and around them also provided insights into the functional and health impacts of CNVs. These findings represent valuable clues to genetic diversity and personalized medicine in the Tunisian population as well as in the ethnically similar populations from North Africa.
Integrated genetic and metabolic landscapes predict vulnerabilities of temozolomide resistant glioblastoma cells
Authors: Immanuel Selva Rupa Christinal , Ghanate Avinash D. , Parmar Dharmeshkumar S. , Yadav Ritu , Uthup Riya , Panchagnula Venkateswarlu , Raghunathan Anu
Published: January 2021

Metabolic reprogramming and its molecular underpinnings are critical to unravel the duality of cancer cell function and chemo-resistance. Here, we use a constraints-based integrated approach to delineate the interplay between metabolism and epigenetics, hardwired in the genome, to shape temozolomide (TMZ) resistance. Differential metabolism was identified in response to TMZ at varying concentrations in both the resistant neurospheroidal (NSP) and the susceptible (U87MG) glioblastoma cell-lines. The genetic basis of this metabolic adaptation was characterized by whole exome sequencing that identified mutations in signaling pathway regulators of growth and energy metabolism. Remarkably, our integrated approach identified rewiring in glycolysis, TCA cycle, malate aspartate shunt, and oxidative phosphorylation pathways. The differential killing of TMZ resistant NSP by Rotenone at low concentrations with an IC50 value of 5 nM, three orders of magnitude lower than for U87MG that exhibited an IC50 value of 1.8 mM was thus identified using our integrated systems-based approach.