bluuebunny/crossref_metadata_2025 huggingface dataset:
MODES: model-based optimization on distributed embedded systems
Authors: Shi Junjie , Bian Jiang , Richter Jakob , Chen Kuan-Hsun , Rahnenführer Jörg , Xiong Haoyi , Chen Jian-Jia
Published: June 2021

The predictive performance of a machine learning model highly depends on the corresponding hyper-parameter setting. Hence, hyper-parameter tuning is often indispensable. Normally such tuning requires the dedicated machine learning model to be trained and evaluated on centralized data to obtain a performance estimate. However, in a distributed machine learning scenario, it is not always possible to collect all the data from all nodes due to privacy concerns or storage limitations. Moreover, if data has to be transferred through low bandwidth connections it reduces the time available for tuning. Model-Based Optimization (MBO) is one state-of-the-art method for tuning hyper-parameters but the application on distributed machine learning models or federated learning lacks research. This work proposes a framework$$\textit{MODES}$$MODESthat allows to deploy MBO on resource-constrained distributed embedded systems. Each node trains an individual model based on its local data. The goal is to optimize the combined prediction accuracy. The presented framework offers two optimization modes: (1)$$\textit{MODES}$$MODES-B considers the whole ensemble as a single black box and optimizes the hyper-parameters of each individual model jointly, and (2)$$\textit{MODES}$$MODES-I considers all models as clones of the same black box which allows it to efficiently parallelize the optimization in a distributed setting. We evaluate$$\textit{MODES}$$MODESby conducting experiments on the optimization for the hyper-parameters of a random forest and a multi-layer perceptron. The experimental results demonstrate that, with an improvement in terms of mean accuracy ($$\textit{MODES}$$MODES-B), run-time efficiency ($$\textit{MODES}$$MODES-I), and statistical stability for both modes,$$\textit{MODES}$$MODESoutperforms the baseline, i.e., carry out tuning with MBO on each node individually with its local sub-data set.
Cost–benefit analysis of flood mitigation measures: a case study employing high-performance hydraulic and damage modelling
Authors: Molinari Daniela , Dazzi Susanna , Gattai Edoardo , Minucci Guido , Pesaro Giulia , Radice Alessio , Vacondio Renato
Published: June 2021

This paper shows a detailed, advanced procedure to implement cost–benefit analyses (CBAs) in order to assess the effectiveness of flood mitigation measures. The town of Lodi (North of Italy) has been selected as a case study for the research work, as it was hit by a large flood in 2002 for which several data are available. In order to compute the benefits, in terms of avoided damage with the mitigation measure in place, micro-scale damage models developed within the Flood-IMPAT + project were used. The great amount of input data for such models comes from results of a two-dimensional river modelling, for what concern the hazard parameters, and from open-source database, to evaluate the vulnerability and the exposure of the hit area. The research highlights that technological-advanced, high-performance hydraulic models allow taking into account a variety of hazard scenarios, with reasonable computational time, supporting the proper accounting of the probabilistic nature of risk in CBAs. Nonetheless, such high-resolution tools support the implementation of micro-scale damage assessment models, which can provide information on the distribution of benefits in the investigated area, increasing the effectiveness of CBAs for policy making.
Comparative phytochemistry of flavaglines (= rocaglamides), a group of highly bioactive flavolignans from Aglaia species (Meliaceae)
Authors: Greger Harald
Published: June 2021

Flavaglines are formed by cycloaddition of a flavonoid nucleus with a cinnamic acid moiety representing a typical chemical character of the genus Aglaia of the family Meliaceae. Based on biosynthetic considerations 148 derivatives are grouped together into three skeletal types representing 77 cyclopenta[b]benzofurans, 61 cyclopenta[bc]benzopyrans, and 10 benzo[b]oxepines. Apart from different hydroxy, methoxy, and methylenedioxy groups of the aromatic rings, important structural variation is created by different substitutions and stereochemistries of the central cyclopentane ring. Putrescine-derived bisamides constitute important building blocks occurring as cyclic 2-aminopyrrolidines or in an open-chained form, and are involved in the formation of pyrimidinone flavaglines. Regarding the central role of cinnamic acid in the formation of the basic skeleton, rocagloic acid represents a biosynthetic precursor from which aglafoline- and rocaglamide-type cyclopentabenzofurans can be derived, while those of the rocaglaol-type are the result of decarboxylation. Broad-based comparison revealed characteristic substitution trends which contribute as chemical markers to natural delimitation and grouping of taxonomically problematic Aglaia species. A wide variety of biological activities ranges from insecticidal, antifungal, antiprotozoal, and anti-inflammatory properties, especially to pronounced anticancer and antiviral activities. The high insecticidal activity of flavaglines is comparable with that of the well-known natural insecticide azadirachtin. Comparative feeding experiments informed about structure–activity relationships and exhibited different substitutions of the cyclopentane ring essential for insecticidal activity. Parallel studies on the antiproliferative activity of flavaglines in various tumor cell lines revealed similar structural prerequisites that let expect corresponding molecular mechanisms. An important structural modification with very high cytotoxic potency was found in the benzofuran silvestrol characterized by an unusual dioxanyloxy subunit. It possessed comparable cytotoxicity to that of the natural anticancer compounds paclitaxel (Taxol®) and camptothecin without effecting normal cells. The primary effect was the inhibition of protein synthesis by binding to the translation initiation factor eIF4A, an ATP-dependent DEAD-box RNA helicase. Flavaglines were also shown to bind to prohibitins (PHB) responsible for regulation of important signaling pathways, and to inhibit the transcriptional factor HSF1 deeply involved in metabolic programming, survival, and proliferation of cancer cells. Flavaglines were shown to be not only promising anticancer agents but gained now also high expectations as agents against emerging RNA viruses like SARS-CoV-2. Targeting the helicase eIF4A with flavaglines was recently described as pan-viral strategy for minimizing the impact of future RNA virus pandemics.
Behavioral Economics and Parent Participation in an Evidence-Based Parenting Program at Scale
Authors: Hill Zoelene , Spiegel Michelle , Gennetian Lisa , Hamer Kai-Ama , Brotman Laurie , Dawson-McClure Spring
Published: June 2021

Evidence-based and culturally relevant parenting programs strengthen adults’ capacity to support children’s health and development. Optimizing parent participation in programs implemented at scale is a prevailing challenge. Our collaborative team of program developers, implementers, and researchers applied insights from the field of behavioral economics (BE) to support parent participation in ParentCorps—a family-centered program delivered as an enhancement to pre-kindergarten—as it scaled in a large urban school district. We designed a bundle of BE-infused parent outreach materials and successfully showed their feasibility in site-level randomized pilot implementation. The site-level study did not show a statistically significant impact on family attendance. A sub-study with a family-level randomization design showed that varying the delivery time of BE-infused digital outreach significantly increased the likelihood of families attending the parenting program. Lessons on the potential value of a BE-infused approach to support outreach and engagement in parenting programs are discussed in the context of scaling up efforts.
The no-free-lunch theorems of supervised learning
Authors: Sterkenburg Tom F. , Grünwald Peter D.
Published: June 2021

The no-free-lunch theorems promote a skeptical conclusion that all possible machine learning algorithms equally lack justification. But how could this leave room for a learning theory, that shows that some algorithms are better than others? Drawing parallels to the philosophy of induction, we point out that the no-free-lunch results presuppose a conception of learning algorithms as purely data-driven. On this conception, every algorithm must have an inherent inductive bias, that wants justification. We argue that many standard learning algorithms should rather be understood as model-dependent: in each application they also require for input a model, representing a bias. Generic algorithms themselves, they can be given a model-relative justification.
Should a higher-order metaphysician believe in properties?
Authors: Liggins David
Published: June 2021

In this paper I take second order-quantification to be asui generisform of quantification, irreducible to first-order quantification, and I examine the implications of doing so for the debate over the existence of properties. Nicholas K. Jones has argued that addingsui generissecond-order quantification to our ideology is enough to establish that properties exist. I argue that Jones does not settle the question of whether there are properties because—like other ontological questions—it is first-order. Then I examine three of the main arguments for the existence of properties. I conclude thatsui generissecond-order quantification defeats the “one over many” argument and that, coupled with second-order predication, it also defeats the reference and quantification arguments.
Blinded by worries: sin taxes and demand for temptation under financial worries
Authors: Burlacu Sergiu , Kažemekaitytė Austėja , Ronzani Piero , Savadori Lucia
Published: June 2021

Imposing “sin” taxes has been the preferred way governments tried to discourage the over-consumption of temptation goods for decades. However numerous evidence shows that consumers exhibit behavioral biases which can affect their reaction to taxes. This paper investigates a potential bias and how it affects demand for temptation: financial worries associated with poverty have been shown to shift attention towards pressing needs, often at the expense of forward-looking decisions. In an online experiment with UK participants, we randomly induce financial worries and ask participants to allocate a budget between basic necessities and temptation goods in an experimental market. We randomly impose “taxes” on temptation by increasing its price. We find that, in the absence of any tax, inducing financial worries lowers demand for temptation, effect stronger for lower-income participants. However, when financial concerns are salient, increasing the tax does not lower demand among lower-income participants. While financial worries might protect against over-consumption of temptation in the absence of tax changes, they also might hurt the poor the most when additional taxes are introduced.
Stress Anisotropy Severely Affects Zinc Phosphate Network Formation
Authors: Sukhomlinov Sergey V. , Müser Martin H.
Published: June 2021

Using density-functional theory based simulations, we study how initially disconnected zinc phosphate molecules respond to different externally imposed deformations. Hybridization changes are observed in all cases, in which the coordination of zinc atoms changes irreversibly from tetrahedral to seesaw and square pyramidal, whereby the system stiffens substantially. The point at which stiff networks are formed does not only depend on the hydrostatic pressure. Stress anisotropy generally reduces the required hydrostatic network formation pressure. Moreover, networks obtained under isotropic deformations turn out stiffer, elastically more isotropic, and lower in energy after decompression than those produced under anisotropic stresses. We also find that the observed stress-memory effects are encoded to a significant degree in the arrangement of atoms in the second neighbor shell of the zinc atoms. These findings refine previously formulated conjectures of pressure-assisted cross-linking in zinc phosphate-based anti-wear films.

Graphical Abstract
Digging deeper into the immunopeptidome: characterization of post-translationally modified peptides presented by MHC I
Authors: Mangalaparthi Kiran K. , Madugundu Anil K. , Ryan Zachary C. , Garapati Kishore , Peterson Jane A. , Dey Gourav , Prakash Amol , Pandey Akhilesh
Published: June 2021

Peptides presented by MHC molecules on the cell surface, or the immunopeptidome, play an important role in the adaptive arm of the immune response. Antigen processing for MHC class I molecules is a ubiquitous pathway present in all nucleated cells which generates and presents peptides of both self and non-self-origin. Peptides with post-translational modifications represent one category of peptides presented by MHC class I molecules. However, owing to the complexity of self-peptides presented by cells, the diversity of peptides with post-translational modifications is not well-studied. In this study, we carried out MHC Class I immunopeptidomics analysis of Loucy T-cell leukemia and A375 malignant melanoma cell line to characterize the diversity of post-translational modifications of MHC class I-bound peptides. Using high resolution mass spectrometry, we identified 25,761 MHC-bound peptides across both cell lines using Bolt and Sequest search engines. The enrichment method was highly specific as ~ 90% of the peptides were of typical length (8–12 amino acids long) and the motifs were expected based on previously reported motifs for MHC I alleles. Among the MHC-bound peptides, we identified phosphorylation as a major post-translational modification followed by deamidation. We observed site-specific localization of these post-translational modifications, at position P4 for phosphorylated peptides and position P3 for deamidated peptides. We identified a smaller number of peptides with acetylated and methylated lysine, possibly due to very low stoichiometric levels of these PTMs compared to phosphorylation and deamidation. Using PEAKS de novo sequencing algorithm, we identified spliced peptides that accounted for ~ 5–7% of MHC-bound peptides that were otherwise similar in their features as normal MHC-bound peptides. We validated the identity of several post-translationally modified peptides and spliced peptides through mass spectrometric analysis of synthetic peptides. Our study confirms post-translationally modified peptides to be present at low stoichiometric levels along with unusual spliced peptides through unbiased identification using high resolution mass spectrometry.
Literature and Medicine
Authors: Mangham Andrew
Published: June 2021

Offering an authoritative account of the relationship between literature and medicine between approximately 1800 and 1900, this volume brings together leading scholars in the field to provide a valuable overview of how two dynamic fields influenced and shaped each during a period of revolutionary change. During the nineteenth century, medicine was being redefined as a subject in which experimental methodologies could transform the healing art, and was simultaneously branching off into new specialisms and subdivisions. Questions addressed in this volume include the influence of physics on poetry, the role of medical professionalism in fiction, the cultural and literary representation of sanitation, and the interdisciplinary nature of controversy and negligence. Along with its sister publication, Literature and Medicine in the Eighteenth Century, this volume offers a major critical overview of the study of literature and medicine.
The "Musica" of Hermannus Contractus
Authors: Snyder John L.
Published: June 2021

Long recognized as one of the most important medieval treatises on music, the Musica of Hermannus Contractus is here presented in a newly revised translation, with commentary reflecting the best current scholarship. A polymath and monk, Hermannus Contractus (1013-54) contributed to the important advancements made in European arts and sciences in the first half of the eleventh century, writing on history, astronomy, and time-keeping devices, among other topics, and composing several chants. His music theory, founded on a systematic treatment of traditional concepts and terminology dating back to the ancient Greeks, is concerned largely with the organization of pitch in Gregorian chant. Hermann's approach stems from Germanic species-based thought, and is marked by a distinction between aspects of form and aspects of position, privileging the latter. He expresses this in terms imported from then-new developments in Italian music theory, thus acting as a nexus for the two traditions. Numerology and number symbolism play significant roles in Hermann's theories, and his critiques of other theorists offer insights into medieval intellectual life. Hermann also uses chant citations and exercises to help his readers apply theory to practice. John L. Snyder's revised edition of Ellinwood's long-standard 1952 text and translation offers a new introduction, including codicological descriptions of the sources; a critical edition of the Latin text with an annotated English translation on facing pages; appendices detailing the documents pertaining to Hermann's life, his citations of plainsong, and his original diastematic notation system; and greatly expanded indexes. Snyder's Musica will serve as the standard version of this major historical document for years to come. Leonard Ellinwood (1905-94) served in the Library of Congress cataloging divisions in music and in the humanities for thirty-five years. He published scholarly works and editions of both medieval music and church music. John L. Snyder is Professor of Music Theory and Musicology at the University of Houston's Moores School of Music.
Unbalanced optimal total variation transport problems and generalized Wasserstein barycenters
Authors: Chung Nhan-Phu , Trinh Thanh-Son
Published: June 2021

In this paper, we establish a Kantorovich duality for unbalanced optimal total variation transport problems. As consequences, we recover a version of duality formula for partial optimal transports established by Caffarelli and McCann; and we also get another proof of Kantorovich–Rubinstein theorem for generalized Wasserstein distance$\widetilde {W}_1^{a,b}$proved before by Piccoli and Rossi. Then we apply our duality formula to study generalized Wasserstein barycenters. We show the existence of these barycenters for measures with compact supports. Finally, we prove the consistency of our barycenters.
Dietary selenium sources differentially regulate selenium concentration, mRNA and protein expression of representative selenoproteins in various tissues of yellow catfish Pelteobagrus fulvidraco
Authors: Xu Xiao-Jian , Zhang Dian-Guang , Zhao Tao , Xu Yi-Huan , Luo Zhi
Published: June 2021

The study was conducted to determine the effects of three dietary Se sources, such as sodium-selenite (S-S), seleno-yeast (S-Y) and seleno-methionine (S-M), on Se concentration, glutathione peroxidase (GPX) and TXNRD activities, and mRNA expression of fifteen representative selenoproteins, and protein expression of four endoplasmic reticulum-resided selenoproteins in a wide range of tissues of yellow catfish. Compared with S-S and S-M groups, dietary S-Y significantly decreased growth performance and feed utilisation of yellow catfish. Dietary Se sources significantly influenced Se contents in the spleen, dorsal muscle and the kidney, GPX activities in spleen, kidney, intestine, muscle and mesenteric fat, and TXNRD activities in the heart, intestine and mesenteric fat. Among ten tested tissues, dietary Se sources influenced mRNA expression of GPX4 and SELENOK in three tissues; GPX3, SELENOS and TXNRD2 in four tissues; SELENOF, SELENON and DIO2 in five tissues; SELENOM, GPX1/2 and TXNRD3 in six tissues; SELENOW in seven tissue and SELENOP and SELENOT in eight tissues. Based on these observations above, S-S and S-M seem to be suitable Se sources for improving growth performance and feed utilisation of yellow catfish. Dietary Se sources differentially influence the expression of selenoproteins in various tissues of yellow catfish. For the first time, we determined the expression of selenoproteins in fish in responses to dietary Se sources, which contributes to a better understanding of the functions and regulatory mechanisms of selenoporteins.
Books, Scribes, and Cultures of Reading in the Shepherd of Hermas
Authors: PROCTOR TRAVIS W.
Published: June 2021

In this article, I analyse how the Shepherd of Hermas constructs an ancient Christian reading culture through concurrent portrayals of Christian reading, copying and book production. I argue that, by portraying its protagonist Hermas as an idealised reader, scribe and auditor, the Shepherd constructs an early Christian reading culture that authenticates Hermas's role as prophet, activates the textual dissemination of the Shepherd and ritualises the practice of Christian auditory ‘reading’. The article closes with ‘Hermas the freedman’, which considers how Hermas's self-presentation as a formerly enslaved person may have connections to the Shepherd's centralisation of ancient reading cultures.
Disciplining the Rich: Tocqueville on Philanthropy and Privilege
Authors: Avramenko Richard , Wolf Brianne
Published: June 2021

This article inquires into the moral successes and failings of the superrich in America. To do this, we turn to Alexis de Tocqueville who outlines a set of expectations for any privileged elite. Drawing from his Old Regime, Memoir on Pauperism, and Democracy in America, we argue that the superrich are obliged to a particular kind of charity, which we specify as philanthropy. To fulfill their philanthropic duties, the superrich must steadfastly attend to three obligations: maintaining their local communities, safeguarding local liberties, and providing moral leadership. In the conclusion, we suggest how the superrich might be disciplined unto this virtue.
Competition, cooperation, and adaptation: The organizational ecology of international organizations in global energy governance
Authors: Downie Christian
Published: June 2021

In policy domains characterised by complexity, international organizations (IOs) with overlapping mandates and governance functions regularly interact in ways that have important implications for global governance. Yet the dynamics of IO interactions remain understudied. This article breaks new ground by building on the theoretical insights of organizational ecology to examine IO competition, cooperation, and adaptation in the domain of energy. Drawing on original empirical data, I consider three related hypotheses: (1) competition between IOs in the same population is likely to centre on material resources; (2) IOs are more likely to cooperate when they have a shared governance goal; and (3) individual IOs can adapt by changing their goals and boundaries. In considering these hypotheses, this article highlights the limits of the organizational ecology approach and the need to broaden it to account for the possibility that IOs do cooperate, and that individual IOs, such as the International Energy Agency, have the capacity to adapt to changes in their environment.
Recording studios as museums? Record producers’ perspectives on German rock studios and accounts of their heritage practice
Authors: Herbst Jan-Peter
Published: June 2021

Recording studios are shrouded in mystery. Some have become sites of pilgrimage; other studios have been converted into heritage museums. These practices are driven by city authorities, commercial heritage institutions or music fans. This interview study gives a voice to an understudied group: record producers and studio owners as the people in charge of popular music creation. Three German rock and metal producers expressed their opinion on the usefulness of studio museums and explained their own heritage practices. Their insights demystify the ‘magical aura’ associated with recording studios, picturing these spaces as places of pressure and anxiety. Hardly convinced of the technologically deterministic ‘magical contamination’ of technical equipment, the producers see little sense in studios as museums. For them, the released record is what counts. To stay in touch with the community and to keep the memory of their work alive, they prefer to use social media.
Media discourses and marketing strategies in the advertising of the pianola
Authors: González Jordi Roquer
Published: June 2021

As a phenomenon of great social relevance between 1900 and 1930, the graphic advertising of the pianola must be considered as one of the first great mass media platforms linked to musical activity and, therefore, the analysis of its discourse offers valuable information about the social construction of the musical world during the first decades of the twentieth century. This article shows the results of an analysis of 200 historical advertisements through which it is possible to trace the origins of some of the current advertising rhetoric and also some of our current ideas about musical activity. In this way, the advertisements studied show some interesting links to the mindset and aesthetic and social conventions of the time but also show us to what degree these discourses are, to a large extent, still valid today.
Mechanical instruments and everyday life: the player piano in Portugal
Authors: Silva João
Published: June 2021

This paper examines player pianos in Portugal between the 1890s and the 1930s. In a small European country with few production facilities, mechanical music developed in a particular way since a local recording industry was expanding rapidly and radio was not yet disseminated. Despite the local market's reliance on imported goods, the music business concentrated on Portuguese pieces. The mechanisation of the piano and its display as a product that embodied modernity illustrates the transformations that took place in Portugal at the beginning of the 20th century. These were reflected in new forms of entertainment, such as cinemas and nightclubs that incorporated new music genres. At the dawn of the century, the leisure market relied on the popular music theatre, which was dominated by Portuguese, French and Spanish music. In the interwar period, English and American pieces made their way into people's lives, transforming the music business.
Private or public adjudication? Procedure, substance and legitimacy
Authors: Kryvoi Yarik
Published: June 2021

This article identifies the essential differences between public and private adjudication and their implications for the legitimacy and efficiency of dispute resolution institutions, as well as the rule of law. Public adjudication comes at a significant cost for the taxpayers but helps secure a consistent body of case law, promotes public policy goals, and allows third parties to know the rules of conduct in advance to prevent undesirable activities. This article shows that procedural rules of these institutions (regardless of whether the procedure is called adjudication or arbitration) differ when it comes to the appointment of adjudicators, their professional background, and how long they serve. Public and private institutions consistently follow different approaches to transparency and confidentiality of proceedings, the application of primarily substantive rules or principles to resolve disagreements, and the extent to which decisions can be reviewed internally or externally. By examining the procedural rules and practices of selected institutions, the article asserts three main claims. First, the choice of public or private adjudication is likely to lead to different procedural outcomes, including the cost of the process and the duration. Second, the legitimacy of any dispute resolution system must rest on both procedural and substantive aspects, while in reality these two are often viewed in isolation. Finally, the article shows how institutions could learn from each other to become more efficient and strengthen their legitimacy.
Explaining power and authority in international courts
Authors: Capps Patrick , Olsen Henrik Palmer
Published: June 2021

It has recently been suggested that the study of international legal life should take an ‘empirical turn’: a turn which has often focused on how patterns of authority emerge and operate in relation to international courts. In what follows it is argued that this empiricism fails to distinguish (for the purposes of sociological inquiry) authority from various other concepts such as power or consensus in the study of international law and courts. This is because this method focuses only on overt signs, such as observable action or statements of intention, and at the level of the sign these concepts are not obviously distinguishable. However, one solution to this problem, which is to collapse socially significant and distinct categories such as authority and consensus into a broad category of ‘power’, requires the adoption of an implausible and inconsistent view of agency in explanations of legal authority. By contrast, and in line with the long-standing interpretivist tradition in sociological and legal method, we claim that in order to interpret the observable signs of compliance to international legal rules and principles as indicative of authority, consensus, or power, it is necessary to interpolate an account of the reasons which give rise to the compliance we observe. This, in turn, explains why international legal doctrine, as an axiological structure, gives rise to the behaviour of its addressees, such as state officials.
Asymptotics of the principal eigenvalue of the Laplacian in 2D periodic domains with small traps
Authors: PAQUIN-LEFEBVRE F. , IYANIWURA S. , WARD M.J
Published: June 2021

We derive and numerically implement various asymptotic approximations for the lowest or principal eigenvalue of the Laplacian with a periodic arrangement of localised traps of small \[\mathcal{O}(\varepsilon )\] spatial extent that are centred at the lattice points of an arbitrary Bravais lattice in \[{\mathbb{R}^2}\]. The expansion of this principal eigenvalue proceeds in powers of \[\nu \equiv - 1/\log (\varepsilon {d_c})\], where dc is the logarithmic capacitance of the trap set. An explicit three-term approximation for this principal eigenvalue is derived using strong localised perturbation theory, with the coefficients in this series evaluated numerically by using an explicit formula for the source-neutral periodic Green’s function and its regular part. Moreover, a transcendental equation for an improved approximation to the principal eigenvalue, which effectively sums all the logarithmic terms in powers of v, is derived in terms of the regular part of the periodic Helmholtz Green’s function. By using an Ewald summation technique to first obtain a rapidly converging infinite series representation for this regular part, a simple Newton iteration scheme on the transcendental equation is implemented to numerically evaluate the improved ‘log-summed’ approximation to the principal eigenvalue. From a numerical computation of the PDE eigenvalue problem defined on the fundamental Wigner–Seitz (WS) cell for the lattice, it is shown that the three-term asymptotic approximation for the principal eigenvalue agrees well with the numerical result only for a rather small trap radius. In contrast, the log-summed asymptotic result provides a very close approximation to the principal eigenvalue even when the trap radius is only moderately small. For a circular trap, the first few transcendental correction terms that further improves the log-summed approximation for the principal eigenvalue are derived. Finally, it is shown numerically that, amongst all Bravais lattices with a fixed area of the primitive cell, the principal eigenvalue is maximised for a regular hexagonal arrangement of traps.
Abnormal origin of the left pulmonary artery from the descending aorta and heterotaxy syndrome: an undescribed phenotypic association
Authors: Moreau de Bellaing Anne , Bonnet Damien , Houyel Lucile
Published: June 2021

Extensive screening in a newborn with prenatal suspicion of VACTERL syndrome identified an anomalous origin of the left pulmonary artery from the descending aorta with an arterial duct and left aortic arch, and normal intra-cardiac anatomy. Other anatomical anomalies suggested heterotaxy syndrome. At one-month-old, re-implantation of the 3.5 mm left pulmonary artery was performed by direct tension-low anastomosis. Post-operative course was complicated by severe left pulmonary atelectasis, and the patient died 20 days later.
Development and Validation of a Cognitive Reserve Index in HIV
Authors: Kaur Navaldeep , Fellows Lesley K. , Brouillette Marie-Josée , Mayo Nancy
Published: June 2021

Objectives:

In the neuroHIV literature, cognitive reserve has most often been operationalized using education, occupation, and IQ. The effects of other cognitively stimulating activities that might be more amenable to interventions have been little studied. The purpose of this study was to develop an index of cognitive reserve in people with HIV, combining multiple indicators of cognitively stimulating lifetime experiences into a single value.

Methods:

The data set was obtained from a Canadian longitudinal study (N = 856). Potential indicators of cognitive reserve captured at the study entry included education, occupation, engagement in six cognitively stimulating activities, number of languages spoken, and social resources. Cognitive performance was measured using a computerized test battery. A cognitive reserve index was formulated using logistic regression weights. For the evidence on concurrent and predictive validity of the index, the measures of cognition and self-reported everyday functioning were each regressed on the index scores at study entry and at the last follow-up [mean duration: 25.9 months (SD 7.2)], respectively. Corresponding regression coefficients and 95% confidence intervals (CIs) were computed.

Results:

Professional sports [odds ratio (OR): 2.9; 95% CI 0.59–14.7], visual and performance arts (any level of engagement), professional/amateur music, complex video gaming and competitive games, and travel outside North America were associated with higher cognitive functioning. The effects of cognitive reserve on the outcomes at the last follow-up visit were closely similar to those at study entry.

Conclusion:

This work contributes evidence toward the relative benefit of engaging in specific cognitively stimulating life experiences in HIV.
Target-date funds and portfolio choice in 401(k) plans
Authors: Mitchell Olivia S. , Utkus Stephen P.
Published: June 2021

Target-date funds in corporate retirement plans grew from $5 billion in 2000 to $734 billion in 2018, partly because federal regulation sanctioned these as default investments in automatic enrollment plans. We show that adopters delegated pension investment decisions to fund managers selected by plan sponsors. Inclusion of these funds in retirement saving menus raised equity shares, boosted bond exposures, curtailed cash/company stock holdings, and reduced idiosyncratic risk. The adoption of low-cost target-date funds may enhance retirement wealth by as much as 50% over a 30-year horizon.
Leaf Wax and Sr‐Nd Isotope Evidence for High‐Latitude Dust Input to the Central South China Sea and Its Implication for Fertilization
Authors: Yang Yi , Bendle James A. , Pancost Richard D. , Yan Yan , Ruan Xiaoyan , Warren Bridget , Lü Xiaoxia , Li Xuejie , Yao Yongjian , Huang Xianyu , Yang Huan , Xie Shucheng
Published: June 2021

Recent time‐series from sediment traps show abnormally high chlorophyll‐a concentrations and primary productivity in the oligotrophic central South China Sea (SCS), especially during wintertime. Here we present new insights from compound‐specific hydrogen isotopic analysis of leaf wax n‐alkanes and Sr‐Nd isotope compositions extracted from four basin‐wide surface sediment transects. We find that the deepest surface sediments in the central basin contain the most depleted n‐alkane hydrogen isotopes, suggesting inputs from higher latitude soils in northern China. This is supported by the Sr‐Nd isotope compositions of the same surface sediments. We propose that aeolian dust is transported by the winter monsoon and might fertilize the phytoplankton bloom in the central SCS. This process may have been enhanced in ancient times when the winter monsoon was stronger, driving both vertical mixing and dust transport to the central basin.
Studying Arctic Fjords with Crowdsourced Science and Sailboats
Authors: Chapman Andrew
Published: June 2021

A new study demonstrates the benefits of crowdsourcing science using sailboats to better understand the impact of melting sea ice in the Arctic.
How Much Carbon Will Peatlands Lose as Permafrost Thaws?
Authors: Thompson Elizabeth
Published: June 2021

How much carbon peatlands may lose—or accumulate—in the future varies from place to place, according to a process-based model.
The PTEN and ATM axis controls the G1/S cell cycle checkpoint and tumorigenesis in HER2-positive breast cancer
Authors: Bassi Christian , Fortin Jerome , Snow Bryan E. , Wakeham Andrew , Ho Jason , Haight Jillian , You-Ten Annick , Cianci Emily , Buckler Luke , Gorrini Chiara , Stambolic Vuk , Mak Tak W.
Published: June 2021

The tumor suppressor PTEN is disrupted in a large proportion of cancers, including in HER2-positive breast cancer, where its loss is associated with resistance to therapy. Upon genotoxic stress, ataxia telangiectasia mutated (ATM) is activated and phosphorylates PTEN on residue 398. To elucidate the physiological role of this molecular event, we generated and analyzed knock-in mice expressing a mutant form of PTEN that cannot be phosphorylated by ATM (PTEN-398A). This mutation accelerated tumorigenesis in a model of HER2-positive breast cancer. Mammary tumors in bi-transgenic mice carrying MMTV-neu and Pten398A were characterized by DNA damage accumulation but reduced apoptosis. Mechanistically, phosphorylation of PTEN at position 398 is essential for the proper activation of the S phase checkpoint controlled by the PI3K–p27Kip1–CDK2 axis. Moreover, we linked these defects to the impaired ability of the PTEN-398A protein to relocalize to the plasma membrane in response to genotoxic stress. Altogether, our results uncover a novel role for ATM-dependent PTEN phosphorylation in the control of genomic stability, cell cycle progression, and tumorigenesis.
RNF20 and RNF40 regulate vitamin D receptor-dependent signaling in inflammatory bowel disease
Authors: Kosinsky Robyn Laura , Zerche Maria , Kutschat Ana Patricia , Nair Asha , Ye Zhenqing , Saul Dominik , von Heesen Maximilian , Friton Jessica J. , Schwarzer Ana Carolina , Paglilla Nadia , Sheikh Shehzad Z. , Wegwitz Florian , Sun Zhifu , Ghadimi Michael , Newberry Rodney D. , Sartor R. Balfour , Faubion William A. , Johnsen Steven A.
Published: June 2021

Despite the identification of several genetic factors linked to increased susceptibility to inflammatory bowel disease (IBD), underlying molecular mechanisms remain to be elucidated in detail. The ubiquitin ligases RNF20 and RNF40 mediate the monoubiquitination of histone H2B at lysine 120 (H2Bub1) and were shown to play context-dependent roles in the development of inflammation. Here, we aimed to examine the function of the RNF20/RNF40/H2Bub1 axis in intestinal inflammation in IBD patients and mouse models. For this purpose, intestinal sections from IBD patients were immunohistochemically stained for H2Bub1. Rnf20 or Rnf40 were conditionally deleted in the mouse intestine and mice were monitored for inflammation-associated symptoms. Using mRNA-seq and chromatin immunoprecipitation (ChIP)-seq, we analyzed underlying molecular pathways in primary intestinal epithelial cells (IECs) isolated from these animals and confirmed these findings in IBD resection specimens using ChIP-seq.The majority (80%) of IBD patients displayed a loss of H2Bub1 levels in inflamed areas and the intestine-specific deletion of Rnf20 or Rnf40 resulted in spontaneous colorectal inflammation in mice. Consistently, deletion of Rnf20 or Rnf40 promoted IBD-associated gene expression programs, including deregulation of various IBD risk genes in these animals. Further analysis of murine IECs revealed that H3K4me3 occupancy and transcription of the Vitamin D Receptor (Vdr) gene and VDR target genes is RNF20/40-dependent. Finally, these effects were confirmed in a subgroup of Crohn’s disease patients which displayed epigenetic and expression changes in RNF20/40-dependent gene signatures. Our findings reveal that loss of H2B monoubiquitination promotes intestinal inflammation via decreased VDR activity thereby identifying RNF20 and RNF40 as critical regulators of IBD.
Characterizing block-copolymer micelles used in nanomedicines via solution static scattering techniques
Authors: Akiba Isamu , Sakurai Kazuo
Published: June 2021

Block copolymers are well recognized as excellent nanotools for delivering hydrophobic drugs. The formulation of such delivery nanoparticles requires robust characterization and clarification of the critical quality attributes correlating with the safety and efficacy of the drug before applying to regulatory authorities for approval. Static solution scattering from block copolymers is one such technique. This paper first outlines the theoretical background and current models for analyzing this scattering and then presents an overview of our recent studies on block copolymers.
Analysis of the ex-vivo transformation of semen, saliva and urine as they dry out using ATR-FTIR spectroscopy and chemometric approach
Authors: Das Tanurup , Harshey Abhimanyu , Srivastava Ankit , Nigam Kriti , Yadav Vijay Kumar , Sharma Kapil , Sharma Arun
Published: June 2021

The ex-vivo biochemical changes of different body fluids also referred as aging of fluids are potential marker for the estimation of Time since deposition. Infrared spectroscopy has great potential to reveal the biochemical changes in these fluids as previously reported by several researchers. The present study is focused to analyze the spectral changes in the ATR-FTIR spectra of three body fluids, commonly encountered in violent crimes i.e., semen, saliva, and urine as they dry out. The whole analytical timeline is divided into relatively slow phase I due to the major contribution of water and faster Phase II due to significant evaporation of water. Two spectral regions i.e., 3200–3400 cm−1 and 1600–1000 cm−1 are the major contributors to the spectra of these fluids. Several peaks in the spectral region between 1600 and 1000 cm−1 showed highly significant regression equation with a higher coefficient of determination values in Phase II in contrary to the slow passing Phase I. Principal component and Partial Least Square Regression analysis are the two chemometric tool used to estimate the time since deposition of the aforesaid fluids as they dry out. Additionally, this study potentially estimates the time since deposition of an offense from the aging of the body fluids at the early stages after its occurrence as well as works as the precursor for further studies on an extended timeframe.
Biochip with multi-planar electrodes geometry for differentiation of non-spherical bioparticles in a microchannel
Authors: Farooq Amina , Butt Nauman Z. , Hassan Umer
Published: June 2021

A biosensor capable of differentiating cells or other microparticles based on morphology finds significant biomedical applications. Examples may include morphological determination in the cellular division process, differentiation of bacterial cells, and cellular morphological variation in inflammation and cancer etc. Here, we present a novel integrated multi-planar microelectrodes geometry design that can distinguish a non-spherical individual particle flowing along a microchannel based on its electrical signature. We simulated multi-planar electrodes design in COMSOL Multiphysics and have shown that the changes in electrical field intensity corresponding to multiple particle morphologies can be distinguished. Our initial investigation has shown that top–bottom electrodes configuration produces significantly enhanced signal strength for a spherical particle as compared to co-planar configuration. Next, we integrated the co-planar and top–bottom configurations to develop a multi-planar microelectrode design capable of electrical impedance measurement at different spatial planes inside a microchannel by collecting multiple output signatures. We tested our integrated multi-planar electrode design with particles of different elliptical morphologies by gradually changing spherical particle dimensions to the non-spherical. The computed electrical signal ratio of non-spherical to spherical particle shows a very good correlation to predict the particle morphology. The biochip sensitivity is also found be independent of orientation of the particle flowing in the microchannel. Our integrated design will help develop the technology that will allow morphological analysis of various bioparticles in a microfluidic channel in the future.
Sarcopenia is associated with poor prognosis after chemoradiotherapy in patients with stage III non-small-cell lung cancer: a retrospective analysis
Authors: Katsui Kuniaki , Ogata Takeshi , Sugiyama Soichi , Yoshio Kotaro , Kuroda Masahiro , Hiraki Takao , Kiura Katsuyuki , Maeda Yoshinobu , Toyooka Shinichi , Kanazawa Susumu
Published: June 2021

We intended to investigate whether muscle and adipose masses were associated with prognosis among patients with stage III non-small-cell lung cancer (NSCLC) who were undergoing chemoradiotherapy (CCRT). We retrospectively explored data of patients with stage III NSCLC who underwent definitive CCRT (≥ 60 Gy) between January 2004 and March 2018 at our hospital. We examined the relationship of overall survival (OS) with body mass index (BMI), skeletal muscle index (SMI), psoas muscle index (PMI), visceral adipose tissue index (VAI), subcutaneous adipose tissue index (SAI), and visceral-to-subcutaneous adipose tissue area ratio (VSR) using log-rank tests for the univariate analysis and Cox proportional hazard models for the multivariate analysis. Overall, 16, 32, and 12 patients had stage IIIA, IIIB, and IIIC NSCLC, respectively. The total radiotherapy dose ranged from 60 Gy/30 fractions to 66 Gy/33 fractions. In the univariate analysis, the performance status (PS), BMI, and SMI were associated with OS, whereas the PMI, VAI, SAI, and VSR were not. In the multivariate analysis, the PS and SMI were associated with OS. The hazard ratios and 95% confidence intervals were 2.91 and 1.28–6.64 for PS, and 2.36 and 1.15–4.85 for SMI, respectively. The 1, 3, and 5-year OS rates were 92.1%, 59.6%, and 51.0% in patients with high SMI, and 63.6%, 53.8%, and 17.9% in patients with low SMI, respectively. The SMI correlated with prognosis in our study population, whereas adipose mass did not. Therefore, sarcopenia should be considered while predicting the OS in such patients.
Mechanochemical methods for the transfer of electrons and exchange of ions: inorganic reactivity from nanoparticles to organometallics
Authors: Fiss Blaine G. , Richard Austin J. , Douglas Georgia , Kojic Monika , Friščić Tomislav , Moores Audrey
Published: June 2021

For inorganic metathesis and reduction reactivity, mechanochemistry is demonstrating great promise towards both nanoparticles and organometallics syntheses.
Microfluidic technologies for immunotherapy studies on solid tumours
Authors: Paterson K. , Zanivan S. , Glasspool R. , Coffelt S. B. , Zagnoni M.
Published: June 2021

Immunotherapy is a powerful and targeted cancer treatment that exploits the body's immune system to attack and eliminate cancerous cells.
Nucleofugality hierarchy, in the aminolysis reaction of 4-cyanophenyl 4-nitrophenyl carbonate and thionocarbonate. Experimental and theoretical study
Authors: Montecinos Rodrigo , Aliaga Margarita E. , Pavez Paulina , Cornejo Patricio , Santos José G.
Published: June 2021

Brønsted plot of the reaction of9with secondary alicyclic amines. The concave upward non-linear plot is in accordance with two parallel mechanistic pathways.