bluuebunny/crossref_metadata_2025 huggingface dataset:
Road construction and its socio-economic and health impact: a case study of Atonsu lake road
Authors: Sackey Lyndon N. A. , Quartey Jeremiah , Nortey Augustus N. N. , Obeng Afia Tiwaa , Okyere Abigail Amoakoatta , Kayoung Phebe Y.
Published: July 2023

The construction of roads has become very popular in our age due to heightened modernization, industrialization and the various benefits reaped from proper road systems. However, construction processes massively contribute to environmental pollution and negatively impact socio-economic activities, necessitating this study. The aim of this paper is to assess the impact of road construction and socioeconomic and health impact using the Atonsu lake road construction as a case study. A mixed research method was employed in the research work. The quantitative method was used for primary data collection through the distribution of questionnaires, which surveyed the perception of inhabitants on the construction activity, and its health and socioeconomic effects. Through a qualitative method, data from the Kumasi south hospital was used to assess the impact of the activity on health. The income levels of inhabitants before and during the construction process were compared to the minimum wage in Ghana to analyze the impact on their socioeconomic lives. The research indicated that road construction has adversely impacted the health of Atonsu lake road inhabitants but saw a decline in the number of cases recorded at the hospital due to restrictions associated with COVID-19 and its accompanying stigmatization, which prevented people from reporting to the hospital. There was also a significant impact on the income levels of the inhabitants, which has a significant correlation with the frequency of client patronage before and during the construction of the road. Findings reinforce the need to greatly consider including effective dust abatement practices and a phase-by-phase implementation of road construction projects to reduce the negative impacts associated with the process.
The Mechanical Tradition of Hero of Alexandria
Authors: Roby Courtney Ann
Published: July 2023

Hero of Alexandria was a figure of great importance not only for ancient technology but also for the medieval and early modern traditions that drew on his work. In this book Courtney Roby presents Hero's key strategies for developing, solving, and contextualizing technical problems, not only in his own lifetime but as an influential tradition of creating accessible technical treatises spanning multiple disciplines. While Hero's historical biography is all but impossible to reconstruct, she examines “Hero” as a corpus, a textual tradition of technical problem-solving capable of incorporating textual transformations like interpolation, epitomization, and translation, as well as intermedial transformation from text to artifact. Key themes include ancient and early modern technical readerships, the relationship between mathematics and mechanics, the materiality of manuscript and printed texts, and the shifting cultural contexts for scientific and technical literature.
Equality Unfulfilled
Authors: Druckman James N. , Sharrow Elizabeth A.
Published: July 2023

The year 1972 is often hailed as an inflection point in the evolution of women's rights. Congress passed Title IX of the Education Amendments of 1972, a law that outlawed sex-based discrimination in education. Many Americans celebrate Title IX for having ushered in an era of expanded opportunity for women's athletics; yet fifty years after its passage, sex-based inequalities in college athletics remain the reality. Equality Unfulfilled explains why. The book identifies institutional roadblocks – including sex-based segregation, androcentric organizational cultures, and overbearing market incentives – that undermine efforts to achieve systemic change. Drawing on surveys with student-athletes, athletic administrators, college coaches, members of the public, and fans of college sports, it highlights how institutions shape attitudes toward gender equity policy. It offers novel lessons not only for those interested in college sports but for everyone seeking to understand the barriers that any marginalized group faces in their quest for equality.
The Queerness of Video Game Music
Authors: Summers Tim
Published: July 2023

Video game music is a significant site of queerness where normative demands are questioned, suspended or loosened. Games resist hegemonic musical logics, challenge musical value systems and use music to complicate essentialist notions of identity. This Element proposes three areas of queerness, each representing different relationships between 'queer design' and 'queer engagement', ranging fromunintentionally resistive to explicit engagement with identity. First, this Element examines musical structures that provide queer temporal alternatives to normative linear development, and interactive systems that reframe the power relationship between musical material and listener. Second, it considers 'retro' or 'chiptune' timbres that queer notions of technological progress to be improvements, rejecting chrononormativity. Finally, the Element discusses music that queers the self/other binary of identity. Games present ways of listening to, engaging with and understanding music that provide opportunities to challenge inherited assumptions and reductive or monolithic values, practices and identities.
The Law of Freedom
Authors: Eisler Jacob
Published: July 2023

The Supreme Court has been at the center of great upheavals in American democracy across the last seventy years. From the end of Jim Crow to the rise of wealth-dominated national campaigns, the Court has battled over if democracy is an egalitarian collaboration to serve the good of all citizens, or a competitive struggle by private interests. In The Law of Freedom, Jacob Eisler questions why the Court has the moral authority to shape democracy at all. Analyzing leading cases through the lens of philosophy and social science, Eisler demonstrates how the soul of election law is a battle between two philosophical understandings of democratic freedom and popular self-rule. This remarkable book reveals that the Court's battle over democracy has shaped how Americans rule themselves, marking election law as the most dramatic judicial intervention in constitutional history.
Reporting Obligations for Attorneys in Money Laundering Cases: Attorney-Client Privilege Under Pressure?
Authors: Hofmann Robin , Lustenberger Livio
Published: July 2023

With the publication of the Panama Papers in 2016, law firms and attorneys came under the spotlight of international anti-money laundering efforts. It became clear that attorneys, protected by the attorney-client privilege, play a significant role in concealing the origin of illicit funds and the constructing of offshore company-schemes. The public outcry prompted legislators to hold these facilitators accountable and to prevent money-laundering activities by imposing reporting obligation on them, whenever there is the suspicion of a client being involved in illicit activities. Unsurprisingly, attorney and professional associations voiced considerable opposition to these legislative efforts claiming an erosion of the attorney client privilege and nothing less than an attack on the rule of law. This article examines the attorney-client privilege from a historical, empirical, and constitutional perspective. A brief analysis of the legal frameworks in Germany and Switzerland exemplifies how reporting obligations affect legal practice and what challenges exist for attorneys. Both countries are considered global hubs for money laundering activities. The legal concepts of holding attorneys accountable in the neighboring countries differ in some respects. In conclusion, it shows that the legal professions successfully managed to widely avoid a ‘responsibilization’.
Statistical non-locality of dynamically coherent structures
Authors: Souza Andre N. , Lutz Tyler , Flierl Glenn R.
Published: July 2023

We analyse a class of stochastic advection problems by conditionally averaging the passive tracer equation with respect to a given flow state. In doing so, we obtain expressions for the turbulent diffusivity as a function of the flow statistics spectrum. When flow statistics are given by a continuous-time Markov process with a finite state space, calculations are amenable to analytic treatment. When the flow statistics are more complex, we show how to approximate turbulent fluxes as hierarchies of finite state space continuous-time Markov processes. The ensemble average turbulent flux is expressed as a linear operator that acts on the ensemble average of the tracer. We recover the classical estimate of turbulent flux as a diffusivity tensor, the components of which are the integrated autocorrelation of the velocity field in the limit that the operator becomes local in space and time.
ROUTINE QUALITY ASSURANCE IN THE SUERC RADIOCARBON LABORATORY
Authors: Tripney B G , Dunbar E , Scott E M , Naysmith P
Published: July 2023

The SUERC Radiocarbon Laboratory reports approximately 3000 unknown samples per year with an additional 1200 samples processed for quality assurance purposes. In addition to the primary OxII standard (SRM-4990C) required for AMS batch normalization, secondary “known-age” standards have been used over many years to evaluate individual batch quality. These have included wood (as prepared alpha-cellulose), barley mash, humic acid, a background mammoth bone, known-age bones, and a whisky sample. In this paper, we present some of the results gathered over routine laboratory operation (for more than 10 years) and examine the results illustrating how they are being used to monitor and quality assure performance. Since many of these samples have also been used in the Glasgow intercomparisons, we will also reflect on the results, as well as the actual and potential uses of such samples.
Inductive Risk and the Legitimacy of Non-Majoritarian Institutions
Authors: Fjørtoft Trym Nohr
Published: July 2023

In political discourse, it is common to claim that non-majoritarian institutions are legitimate because they are technical and value-free. Even though most analysts disagree, many arguments for non-majoritarian legitimacy rest on claims that work best if institutions are, in fact, value-free. This paper develops a novel standard for non-majoritarian legitimacy. It builds on the rich debate over the value-free ideal in philosophy of science, which has not, so far, been applied systematically to political theory literature on non-majoritarian institutions. This paper suggests that the argument from inductive risk, a strong argument against the value-free ideal, (1) shows why a naive claim to value freedom is a poor general foundation for non-majoritarian legitimacy; (2) provides a device to assess the degree of democratic value inputs required for an institution to be legitimate; which (3) shows the conditions under which a claim to technical legitimacy might still be normatively acceptable.
Early access schemes for innovative health technologies: the views of international stakeholders
Authors: Farmer Caroline , O’Toole Brian , Barnish Maxwell S. , Trigg Laura A. , Hayward Samuel , Crathorne Louise , Kasten Zelie , Spoors John , Melendez-Torres G. J.
Published: July 2023

Objectives

Early access schemes (EASs) are approaches used by payers to balance and facilitate earlier patient access to innovative health technologies while evidence generation is ongoing. Schemes require investment from payers and are associated with significant risk since not all technologies will be routinely reimbursed. The purpose of this study was to gain the perspectives of policy experts about the key challenges for EASs and potential solutions for their optimal design and implementation.

Methods

Two virtual workshops were convened including (i) UK-based policy experts (England, Wales, and Scotland) and (ii) representatives from multiple healthcare systems (England, France, Sweden, Canada, Poland, and Norway). Participants were encouraged to share their experiences with EASs in their healthcare system and highlight key challenges for policy makers. Discussions were transcribed and analyzed using framework analysis.

Results

Participants agreed that EASs have value when targeted toward innovative technologies with the potential for significant clinical benefit in an area of high unmet need. Participants discussed potential solutions to the challenges faced by payers implementing EASs, including defining eligibility criteria, supporting evidence generation, and approaches to reimbursement.

Conclusions

Participants agreed that EASs are one possible solution for their healthcare systems and have the potential to deliver significant clinical value to patients. However, widespread adoption of EASs is limited due to concerns about the risks for patients and healthcare budgets, further solutions are needed to deliver EASs for targeted therapies.
How does linguistic context influence word learning?
Authors: ALHAMA Raquel G. , ROWLAND Caroline F. , KIDD Evan
Published: July 2023

While there are well-known demonstrations that children can use distributional information to acquire multiple components of language, the underpinnings of these achievements are unclear. In the current paper, we investigate the potential pre-requisites for a distributional learning model that can explain how children learn their first words. We review existing literature and then present the results of a series of computational simulations with Vector Space Models, a type of distributional semantic model used in Computational Linguistics, which we evaluate against vocabulary acquisition data from children. We focus on nouns and verbs, and we find that: (i) a model with flexibility to adjust for the frequency of events provides a better fit to the human data, (ii) the influence of context words is very local, especially for nouns, and (iii) words that share more contexts with other words are harder to learn.
Exploring the effect of cryopreservation in assisted reproductive technology and potential epigenetic risk
Authors: Sciorio Romualdo , Campos Gerard , Tramontano Luca , Bulletti Francesco M. , Baldini Giorgio M. , Vinciguerra Marina
Published: July 2023

Since the birth of the first baby by in vitro fertilization in 1978, more than 9 million children have been born worldwide using medically assisted reproductive treatments. Fertilization naturally takes place in the maternal oviduct where unique physiological conditions enable the early healthy development of the embryo. During this dynamic period of early development major waves of epigenetic reprogramming, crucial for the normal fate of the embryo, take place. Increasingly, over the past 20 years concerns relating to the increased incidence of epigenetic anomalies in general, and genomic-imprinting disorders in particular, have been raised following assisted reproduction technology (ART) treatments. Epigenetic reprogramming is particularly susceptible to environmental conditions during the periconceptional period and non-physiological conditions such as ovarian stimulation, in vitro fertilization and embryo culture, as well as cryopreservation procedure, might have the potential to independently or collectively contribute to epigenetic dysregulation. Therefore, this narrative review offers a critical reappraisal of the evidence relating to the association between embryo cryopreservation and potential epigenetic regulation and the consequences on gene expression together with long-term consequences for offspring health and wellbeing. Current literature suggests that epigenetic and transcriptomic profiles are sensitive to the stress induced by vitrification, in terms of osmotic shock, temperature and pH changes, and toxicity of cryoprotectants, it is therefore, critical to have a more comprehensive understanding and recognition of potential unanticipated iatrogenic-induced perturbations of epigenetic modifications that may or may not be a consequence of vitrification.
Prävalenz von neuropsychiatrischen Symptomen bei Menschen mit Demenz in der stationären Langzeitpflege
Authors: Hüsken Johann-Moritz , Halek Margareta , Holle Daniela , Dichter Martin N.
Published: July 2023

Zusammenfassung: Hintergrund: Im Verlauf einer Demenz entwickeln die meisten Betroffenen neuropsychiatrische Symptome. Bisher gibt es kaum Untersuchungen zu den spezifischen Ausprägungsformen dieser in der stationären Langzeitpflege. Fragestellung/Ziel: Differenzierte Untersuchung der Prävalenz und Ausprägungsformen von neuropsychiatrischen Symptomen bei Menschen mit Demenz in der stationären Langzeitpflege. Methoden: Durch eine Sekundäranalyse von Querschnittsdaten der Forschungsprojekte LebenQD I & II sowie FallDem wurde die Prävalenz von neuropsychiatrischen Symptomen bei Menschen mit Demenz in der stationären Langzeitpflege untersucht. Diese wurden mit dem Neuropsychiatrischen Inventar – Version Pflegeheim erhoben. In die Analyse sind Daten von 699 Menschen mit Demenz aus insgesamt 21 Langzeitpflegeeinrichtungen in Nordrhein-Westfalen eingeflossen. Ergebnisse: Die höchste Prävalenz zeigen die Symptome Erregung/Aggression (36%), Depression/Dysphorie (33%), Apathie/Gleichgültigkeit (33%), Reizbarkeit/Labilität (30%) und Abweichendes motorisches Verhalten (27%). Die Symptome Halluzination (9%) und Euphorie/Hochstimmung (6%) haben die geringste Prävalenz. Schlussfolgerungen: Die hohe Prävalenz spezifischer neuropsychiatrischer Symptome und deren Ausprägungsformen bei Menschen mit Demenz verdeutlicht den Bedarf pflegerischer- oder psychosozialer Interventionen, um den Gründen für das Auftreten der Symptome entgegenzuwirken.
The Thermal Regime of NW Canada and Alaska, and Tectonic and Seismicity Consequences
Authors: Hyndman R. D.
Published: July 2023

NW Canada and Alaska are the continuation of the North American Cordillera through Mexico, western USA and western Canada. I show that they have similar thermal regimes and thermal control of tectonics and seismicity. I first summarize the multiple constraints to crust and upper mantle temperatures and then discuss some consequences. There are bimodal crust and upper mantle temperatures characteristic of most subduction zones: cool forearc, uniformly hot backarc (Yukon Composite Terrane to Southern Brooks Range, and Mackenzie Mountains), and stable cratonic backstops (Arctic Alaska Terrane and Canadian Shield). The main constraints are as follows: (a) Heat flow measurements, (b) Temperature‐dependent upper mantle velocities and seismic attenuation, (c) Temperature‐dependent topographic elevations; thermal isostasy, (d) Depth and temperature of the seismic lithosphere‐asthenosphere boundary (LAB), (e) Origin temperature and depth of craton kimberlite xenoliths, (f) Geochemically inferred source temperature and depth of recent volcanic rocks. (g) Depth to the magnetic Curie temperature, (h) Depth extent of seismicity. The backarc lithosphere is thin, LAB at 50–85 km and ∼1,350°C ± 25°C. Moho temperatures at 35 km are 850°C ± 100°C compared to cool cratonic areas of 400°C–500°C. The consequences include the following: (a) Thin and weak backarc lithosphere that accommodates pervasive tectonic deformation indicated by wide‐spread seismicity and GPS‐defined motions, in contrast to the stable cratonic regions; (b) Weak backarc lower crust that flattens the Moho and allows detachment and thrusting of the upper crust over the cold strong Arctic Alaska Terrane and Canadian Shield. This article provides a model for how to estimate deep temperatures from multiple constraints.
A Novel Low‐Loss Planar PRGW Crossover Design for 5G Applications
Authors: Mousavirazi Zahra , Ali Mohamed Mamdouh M. , Rezaei Pejman , Sebak Abdel R. , Denidni Tayeb A.
Published: July 2023

In this paper, a planar 0‐dB crossover using printed ridge gap waveguide (PRGW) technology is proposed and designed for millimeter‐wave applications. PRGW as a quasi‐TE mode is considered as the modern guiding technology at high frequencies and for the 5G and other upcoming communications. A prototype of the proposed PRGW crossover working around 30 GHz is fabricated and measured to validate the simulated results. Comparing simulated with measured results, a good agreement is observed. The measured results demonstrate that the designed crossover offers an insertion loss of better than 0.5 dB over the whole operating frequency bandwidth from 29 to 31 GHz where the return loss level is better than 15 dB and the isolation level is less than −13 dB. Compared with the other reported crossover structures, the designed PRGW crossover features a wider bandwidth with a smaller and planar configuration.
Fundamental Shift From Summer to Winter of Holocene Rainfall Regime in the Tropics
Authors: Lan Jianghu , Cheng Jun , Chawchai Sakonvan , Liu Xingxing , Cheng Peng , Liu Yitao , Leknettip Smith , Yan Hong , Sun Youbin , Dong Jibao , Xu Hai , Ma Xiaolin , Zhang Haiwei , Lu Fengyan , Ma Libin , Tan Liangcheng , Liu Zhengyu
Published: July 2023

The seasonal rainfall regime is a key factor control on local ecological and social processes and is commonly thought to be stable under long‐term climate changes. Here we present a unique high‐resolution rainfall record from the Thai‐Malay Peninsula, combined with a state‐of‐the‐art transient climate simulation, demonstrating a fundamental rainfall regime shift from summer to winter during the Holocene. Transient model simulation and new sensitivity experiments further reveal that westward migration of the boundary between summer and winter rainfall regimes results in a summer to winter rainfall regime shift forced by distinct changes in summer and winter monsoons. Our findings suggest that the seasonal rainfall regime could be unstable under climate change around the boundaries of rainfall regimes in the tropics and possibly worldwide, which might be more critical for shaping both past and future ecological environments.
Plasticity of neuronal dynamics in the lateral habenula for cue-punishment associative learning
Authors: Congiu Mauro , Mondoloni Sarah , Zouridis Ioannis S. , Schmors Lisa , Lecca Salvatore , Lalive Arnaud L. , Ginggen Kyllian , Deng Fei , Berens Philipp , Paolicelli Rosa Chiara , Li Yulong , Burgalossi Andrea , Mameli Manuel
Published: July 2023

The brain’s ability to associate threats with external stimuli is vital to execute essential behaviours including avoidance. Disruption of this process contributes instead to the emergence of pathological traits which are common in addiction and depression. However, the mechanisms and neural dynamics at the single-cell resolution underlying the encoding of associative learning remain elusive. Here, employing a Pavlovian discrimination task in mice we investigate how neuronal populations in the lateral habenula (LHb), a subcortical nucleus whose excitation underlies negative affect, encode the association between conditioned stimuli and a punishment (unconditioned stimulus). Large population single-unit recordings in the LHb reveal both excitatory and inhibitory responses to aversive stimuli. Additionally, local optical inhibition prevents the formation of cue discrimination during associative learning, demonstrating a critical role of LHb activity in this process. Accordingly, longitudinal in vivo two-photon imaging tracking LHb calcium neuronal dynamics during conditioning reveals an upward or downward shift of individual neurons’ CS-evoked responses. While recordings in acute slices indicate strengthening of synaptic excitation after conditioning, support vector machine algorithms suggest that postsynaptic dynamics to punishment-predictive cues represent behavioral cue discrimination. To examine the presynaptic signaling in LHb participating in learning we monitored neurotransmitter dynamics with genetically-encoded indicators in behaving mice. While glutamate, GABA, and serotonin release in LHb remain stable across associative learning, we observe enhanced acetylcholine signaling developing throughout conditioning. In summary, converging presynaptic and postsynaptic mechanisms in the LHb underlie the transformation of neutral cues in valued signals supporting cue discrimination during learning.
Novel effects of Ras-MAPK pathogenic variants on the developing human brain and their link to gene expression and inhibition abilities
Authors: Rai Bhavana , Naylor Paige E. , Siqueiros-Sanchez Monica , Wintermark Max , Raman Mira M. , Jo Booil , Reiss Allan L. , Green Tamar
Published: July 2023

The RASopathies are genetic syndromes associated with pathogenic variants causing dysregulation of the Ras/mitogen-activated protein kinase (Ras-MAPK) pathway, essential for brain development, and increased risk for neurodevelopmental disorders. Yet, the effects of most pathogenic variants on the human brain are unknown. We examined: (1) How Ras-MAPK activating variants ofPTPN11/SOS1protein-coding genes affect brain anatomy. (2) The relationship betweenPTPN11gene expression levels and brain anatomy, and (3) The relevance of subcortical anatomy to attention and memory skills affected in the RASopathies. We collected structural brain MRI and cognitive-behavioral data from 40 pre-pubertal children with Noonan syndrome (NS), caused byPTPN11(n = 30) orSOS1(n = 10) variants (age 8.53 ± 2.15, 25 females), and compared them to 40 age- and sex-matched typically developing controls (9.24 ± 1.62, 27 females). We identified widespread effects of NS on cortical and subcortical volumes and on determinants of cortical gray matter volume, surface area (SA), and cortical thickness (CT). In NS, we observed smaller volumes of bilateral striatum, precentral gyri, and primary visual area (d’s < −0.8), and extensive effects on SA (d’s > |0.8|) and CT (d’s > |0.5|) relative to controls. Further, SA effects were associated with increasingPTPN11gene expression, most prominently in the temporal lobe. Lastly,PTPN11variants disrupted normative relationships between the striatum and inhibition functioning. We provide evidence for the effects of Ras-MAPK pathogenic variants on striatal and cortical anatomy as well as links betweenPTPN11gene expression and cortical SA increases, and striatal volume and inhibition skills. These findings provide essential translational information on the Ras-MAPK pathway’s effect on human brain development and function.
Chalcogen-bridged coordination polymer for the photocatalytic activation of aryl halides
Authors: Zeng Le , Zhang Tiexin , Liu Renhai , Tian Wenming , Wu Kaifeng , Zhu Jingyi , Wang Zhonghe , He Cheng , Feng Jing , Guo Xiangyang , Douka Abdoulkader Ibro , Duan Chunying
Published: July 2023

The ability to deliver electrons is vital for dye-based photocatalysts. Conventionally, the aromatic stacking-based charge-transfer complex increases photogenerated electron accessibility but decreases the energy of excited-state dyes. To circumvent this dilemma, here we show a strategy by tuning the stacking mode of dyes. By decorating naphthalene diimide with S-bearing branches, the S···S contact-linked naphthalene diimide string is created in coordination polymer, thereby enhancing electron mobility while simultaneously preserving competent excited-state reducing power. This benefit, along with in situ assembly between naphthalene diimide strings and exogenous reagent/reactant, improves the accessibility of short-lived excited states during consecutive photon excitation, resulting in greater efficiency in photoinduced electron-transfer activation of inert bonds in comparison to other coordination polymers with different dye-stacking modes. This heterogeneous approach is successfully applied in the photoreduction of inert aryl halides and the successive formation of CAr−C/S/P/B bonds with potential pharmaceutical applications.
Characterizing the evolution and phenotypic impact of ampliconic Y chromosome regions
Authors: Lucotte Elise A. , Guðmundsdóttir Valdís Björt , Jensen Jacob M. , Skov Laurits , Macià Moisès Coll , Almstrup Kristian , Schierup Mikkel H. , Helgason Agnar , Stefansson Kari
Published: July 2023

A major part of the human Y chromosome consists of palindromes with multiple copies of genes primarily expressed in testis, many of which have been claimed to affect male fertility. Here we examine copy number variation in these palindromes based on whole genome sequence data from 11,527 Icelandic men. Using a subset of 7947 men grouped into 1449 patrilineal genealogies, we infer 57 large scale de novo copy number mutations affecting palindrome 1. This corresponds to a mutation rate of 2.34 × 10−3 mutations per meiosis, which is 4.1 times larger than our phylogenetic estimate of the mutation rate (5.72 × 10−4), suggesting that de novo mutations on the Y are lost faster than expected under neutral evolution. Although simulations indicate a selection coefficient of 1.8% against non-reference copy number carriers, we do not observe differences in fertility among sequenced men associated with their copy number genotype, but we lack statistical power to detect differences resulting from weak negative selection. We also perform association testing of a diverse set of 341 traits to palindromic copy number without any significant associations. We conclude that large-scale palindrome copy number variation on the Y chromosome has little impact on human phenotype diversity.
Identification of the SARS-unique domain of SARS-CoV-2 as an antiviral target
Authors: Qin Bo , Li Ziheng , Tang Kaiming , Wang Tongyun , Xie Yubin , Aumonier Sylvain , Wang Meitian , Yuan Shuofeng , Cui Sheng
Published: July 2023

SARS-CoV-2 nsp3 is essential for viral replication and host responses. The SARS-unique domain (SUD) of nsp3 exerts its function through binding to viral and host proteins and RNAs. Herein, we show that SARS-CoV-2 SUD is highly flexible in solution. The intramolecular disulfide bond of SARS-CoV SUD is absent in SARS-CoV-2 SUD. Incorporating this bond in SARS-CoV-2 SUD allowed crystal structure determination to 1.35 Å resolution. However, introducing this bond in SARS-CoV-2 genome was lethal for the virus. Using biolayer interferometry, we screened compounds directly binding to SARS-CoV-2 SUD and identified theaflavin 3,3’-digallate (TF3) as a potent binder, Kd 2.8 µM. TF3 disrupted the SUD-guanine quadruplex interactions and exhibited anti-SARS-CoV-2 activity in Vero E6-TMPRSS2 cells with an EC50 of 5.9 µM and CC50 of 98.5 µM. In this work, we provide evidence that SARS-CoV-2 SUD harbors druggable sites for antiviral development.
How to make climate-neutral aviation fly
Authors: Sacchi Romain , Becattini Viola , Gabrielli Paolo , Cox Brian , Dirnaichner Alois , Bauer Christian , Mazzotti Marco
Published: July 2023

The European aviation sector must substantially reduce climate impacts to reach net-zero goals. This reduction, however, must not be limited to flight CO2 emissions since such a narrow focus leaves up to 80% of climate impacts unaccounted for. Based on rigorous life-cycle assessment and a time-dependent quantification of non-CO2 climate impacts, here we show that, from a technological standpoint, using electricity-based synthetic jet fuels and compensating climate impacts via direct air carbon capture and storage (DACCS) can enable climate-neutral aviation. However, with a continuous increase in air traffic, synthetic jet fuel produced with electricity from renewables would exert excessive pressure on economic and natural resources. Alternatively, compensating climate impacts of fossil jet fuel via DACCS would require massive CO2 storage volumes and prolong dependence on fossil fuels. Here, we demonstrate that a European climate-neutral aviation will fly if air traffic is reduced to limit the scale of the climate impacts to mitigate.
Spatiotemporal transcriptomic maps of whole mouse embryos at the onset of organogenesis
Authors: Sampath Kumar Abhishek , Tian Luyi , Bolondi Adriano , Hernández Amèlia Aragonés , Stickels Robert , Kretzmer Helene , Murray Evan , Wittler Lars , Walther Maria , Barakat Gabriel , Haut Leah , Elkabetz Yechiel , Macosko Evan Z. , Guignard Léo , Chen Fei , Meissner Alexander
Published: July 2023

Spatiotemporal orchestration of gene expression is required for proper embryonic development. The use of single-cell technologies has begun to provide improved resolution of early regulatory dynamics, including detailed molecular definitions of most cell states during mouse embryogenesis. Here we used Slide-seq to build spatial transcriptomic maps of complete embryonic day (E) 8.5 and E9.0, and partial E9.5 embryos. To support their utility, we developed sc3D, a tool for reconstructing and exploring three-dimensional ‘virtual embryos’, which enables the quantitative investigation of regionalized gene expression patterns. Our measurements along the main embryonic axes of the developing neural tube revealed several previously unannotated genes with distinct spatial patterns. We also characterized the conflicting transcriptional identity of ‘ectopic’ neural tubes that emerge in Tbx6 mutant embryos. Taken together, we present an experimental and computational framework for the spatiotemporal investigation of whole embryonic structures and mutant phenotypes.
High-density Surface and Intramuscular EMG Data from the Tibialis Anterior During Dynamic Contractions
Authors: Bradford J. Cortney , Tweedell Andrew , Leahy Logan
Published: July 2023

Valid approaches for interfacing with and deciphering neural commands related to movement are critical to understanding muscular coordination and developing viable prostheses and wearable robotics. While electromyography (EMG) has been an established approach for mapping neural input to mechanical output, there is a lack of adaptability to dynamic environments due to a lack of data from dynamic movements. This report presents data consisting of simultaneously recorded high density surface EMG, intramuscular EMG, and joint dynamics from the tibialis anterior during static and dynamic muscle contractions. The dataset comes from seven subjects performing three to five trials each of different types of muscle contractions, both static (isometric) and dynamic (isotonic and isokinetic). Each subject was seated in an isokinetic dynamometer such that ankle movement was isolated and instrumented with four fine wire electrodes and a 126-electrode surface EMG grid. This data set can be used to (i) validate methods for extracting neural signals from surface EMG, (ii) develop models for predicting torque output, or (iii) develop classifiers for movement intent.
Encoding integers and rationals on neuromorphic computers using virtual neuron
Authors: Date Prasanna , Kulkarni Shruti , Young Aaron , Schuman Catherine , Potok Thomas , Vetter Jeffrey
Published: July 2023

Neuromorphic computers emulate the human brain while being extremely power efficient for computing tasks. In fact, they are poised to be critical for energy-efficient computing in the future. Neuromorphic computers are primarily used in spiking neural network–based machine learning applications. However, they are known to be Turing-complete, and in theory can perform all general-purpose computation. One of the biggest bottlenecks in realizing general-purpose computations on neuromorphic computers today is the inability to efficiently encode data on the neuromorphic computers. To fully realize the potential of neuromorphic computers for energy-efficient general-purpose computing, efficient mechanisms must be devised for encoding numbers. Current encoding mechanisms (e.g., binning, rate-based encoding, and time-based encoding) have limited applicability and are not suited for general-purpose computation. In this paper, we present the virtual neuron abstraction as a mechanism for encoding and adding integers and rational numbers by using spiking neural network primitives. We evaluate the performance of the virtual neuron on physical and simulated neuromorphic hardware. We estimate that the virtual neuron could perform an addition operation using just 23 nJ of energy on average with a mixed-signal, memristor-based neuromorphic processor. We also demonstrate the utility of the virtual neuron by using it in some of the μ-recursive functions, which are the building blocks of general-purpose computation.
Study on the fastening characteristics of preformed helical fittings considering the surface effect of transmission lines
Authors: Zhongbin Lv , Guanghui Liu , Fangyu Li , Chuan Wu , Yaguang Tao , Jufang Liu , Zhongfei Ye , Xiaohui Liu , Yuntao Sun , Bo Yan
Published: July 2023

Because of their superior mechanical properties, preformed helical fittings are widely used in UHV transmission lines. However, they easily slip and become loose under extreme environments, so it is very important to study the fastening characteristics of preformed helical fittings. According to the stress characteristics of preformed helical fittings, a parametric finite element model including a core and preformed armor rods was established. Finally, the finite element model calculation was verified by comparing it with the test results. In this paper, the influences of the preformed armor rod diameter, pitch, length and forming aperture on the fastening characteristics were investigated. The numerical simulation results showed that the smaller the forming aperture of preformed armor rods, the larger the grip force. However, a small forming aperture is inconvenient to install, and too large of a grip force on the core easily leads to core damage. With the increase in the preformed armor rod length, the grip force increased gradually and linearly, and the increase slowed after the pitch number reached 9. The larger the pitch, the smaller the grip force of the preformed helical fittings. The fastening characteristics of preformed armor rods with slightly larger diameters were better and the fourth power of the diameter of the preformed armor rods has a linear relationship with the grip force.
The growth of the mastoid volume in children with a cochlear implant
Authors: Tirkkonen Minna , Iso-Mustajärvi Matti , Dhanasingh Anandhan , Linder Pia , Myller Katariina , Dietz Aarno
Published: July 2023

The aim of this study was to understand the mastoid volume development in children who undergo cochlear implantation surgery. Cochlear implant (CI) database of our clinic (Kuopio University Hospital) was reviewed for computed tomography (CT) images of CI patients (age under 12 years at the time of implantation) with a minimum time interval of twelve months between their pre- and postoperative CT. Eight patients (nine ears) were found eligible for inclusion. Three linear measurements were taken by using picture archiving and communication systems (PACS) software and the volume of the MACS was measured with Seg 3D software. The mastoid volume increased on average 817.5 mm3 between the pre- and the postoperative imaging time point. The linear distances measured between anatomical points like the round window (RW)- bony ear canal (BEC), the RW-sigmoid sinus (SS), the BEC-SS, and the mastoid tip (MT)-superior semicircular canal (SSC) increased significantly with the age of the patient at both the pre-op and post-op time points. The linear measurements between key anatomical points and mastoid volume showed a positive linear correlation. The correlation between linear measurement and volume were significant between the MT-SSC (r = 0.706, p = 0.002), RW-SS (r = 0.646, p = 0.005) and RW-BEC (r = 0.646, p = 0.005). Based on our findings from the CI implanted patients and comparing it with the previous literature findings from non-CI implanted patients, we could say that the CI surgery seem to have no effect on the development of mastoid volume in children.
Application of ultrasensitive digital ELISA for p24 enables improved evaluation of HIV-1 reservoir diversity and growth kinetics in viral outgrowth assays
Authors: Kuzmichev Yury V. , Lackman-Smith Carol , Bakkour Sonia , Wiegand Ann , Bale Michael J. , Musick Andrew , Bernstein Wendy , Aronson Naomi , Ake Julie , Tovanabutra Sodsai , Stone Mars , Ptak Roger G. , Kearney Mary F. , Busch Michael P. , Wonderlich Elizabeth R. , Kulpa Deanna A.
Published: July 2023

The advent of combined antiretroviral therapy (cART) has been instrumental in controlling HIV-1 replication and transmission and decreasing associated morbidity and mortality. However, cART alone is not able to cure HIV-1 due to the presence of long-lived, latently infected immune cells, which re-seed plasma viremia when cART is interrupted. Assessment of HIV-cure strategies using ex vivo culture methods for further understanding of the diversity of reactivated HIV, viral outgrowth, and replication dynamics are enhanced using ultrasensitive digital ELISA based on single-molecule array (Simoa) technology to increase the sensitivity of endpoint detection. In viral outgrowth assays (VOA), exponential HIV-1 outgrowth has been shown to be dependent upon initial virus burst size surpassing a critical growth threshold of 5100 HIV-1 RNA copies. Here, we show an association between ultrasensitive HIV-1 Gag p24 concentrations and HIV-1 RNA copy number that characterize viral dynamics below the exponential replication threshold. Single-genome sequencing (SGS) revealed the presence of multiple identical HIV-1 sequences, indicative of low-level replication occurring below the threshold of exponential outgrowth early during a VOA. However, SGS further revealed diverse related HIV variants detectable by ultrasensitive methods that failed to establish exponential outgrowth. Overall, our data suggest that viral outgrowth occurring below the threshold necessary for establishing exponential growth in culture does not preclude replication competence of reactivated HIV, and ultrasensitive detection of HIV-1 p24 may provide a method to detect previously unquantifiable variants. These data strongly support the use of the Simoa platform in a multi-prong approach to measuring latent viral burden and efficacy of therapeutic interventions aimed at an HIV-1 cure.
Multimodal investigation of electronic transport in PTMA and its impact on organic radical battery performance
Authors: Daniel Davis Thomas , Oevermann Steffen , Mitra Souvik , Rudolf Katharina , Heuer Andreas , Eichel Rüdiger-A. , Winter Martin , Diddens Diddo , Brunklaus Gunther , Granwehr Josef
Published: July 2023

Organic radical batteries (ORBs) represent a viable pathway to a more sustainable energy storage technology compared to conventional Li-ion batteries. For further materials and cell development towards competitive energy and power densities, a deeper understanding of electron transport and conductivity in organic radical polymer cathodes is required. Such electron transport is characterised by electron hopping processes, which depend on the presence of closely spaced hopping sites. Using a combination of electrochemical, electron paramagnetic resonance (EPR) spectroscopic, and theoretical molecular dynamics as well as density functional theory modelling techniques, we explored how compositional characteristics of cross-linked poly(2,2,6,6-tetramethyl-1-piperidinyloxy-4-yl methacrylate) (PTMA) polymers govern electron hopping and rationalise their impact on ORB performance. Electrochemistry and EPR spectroscopy not only show a correlation between capacity and the total number of radicals in an ORB using a PTMA cathode, but also indicates that the state-of-health degrades about twice as fast if the amount of radical is reduced by 15%. The presence of up to 3% free monomer radicals did not improve fast charging capabilities. Pulsed EPR indicated that these radicals readily dissolve into the electrolyte but a direct effect on battery degradation could not be shown. However, a qualitative impact cannot be excluded either. The work further illustrates that nitroxide units have a high affinity to the carbon black conductive additive, indicating the possibility of its participation in electron hopping. At the same time, the polymers attempt to adopt a compact conformation to increase radical–radical contact. Hence, a kinetic competition exists, which might gradually be altered towards a thermodynamically more stable configuration by repeated cycling, yet further investigations are required for its characterisation.
Containment of sulfate in leachate as gypsum (CaSO4·2H2O) mineral formation in bio-cemented sand via enzyme-induced carbonate precipitation
Authors: Kim Junghoon , Kim Daehyun , Yun Tae Sup
Published: July 2023

Enzymatically induced carbonate precipitation (EICP) using urea hydrolysis is a well-known bio-cementation process that not only promotes the precipitation of calcium carbonate (CaCO3) but can provide excess calcium cations for further reaction depending on the substrate constituents and reaction stage. This study presents the EICP recipe to contain sulfate ions in landfill leachate sufficiently using remaining calcium cations and a series of tests were conducted to validate its ability to retain sulfates. The reaction rate for 1 M CaCl2and 1.5 M urea was identified by controlling the purified urease content and the curing time of the EICP process. The results showed that 0.3 g/L of purified urease produced 46% CaCO3and reduced sulfate ions by 77% after 3 days of curing. The shear stiffness in EICP-treated sand was enhanced 13 times by CaCO3precipitation followed by 1.12 times increment due to subsequent precipitation of gypsum (CaSO4·2H2O) crystals implying sulfate containment. A cost-efficient EICP treatment using soybean crude urease instead of lab-grade purified urease exhibited lower sulfate removal efficiency (i.e., 18%) with only nominal formation of gypsum in the EICP-treated sand. The addition of gypsum powder was effective in increasing sulfate removal by 40% when soybean crude urease was used for EICP.
A model eye for fluorescent characterization of retinal cultures and tissues
Authors: Ferraro G. , Gigante Y. , Pitea M. , Mautone L. , Ruocco G. , Di Angelantonio S. , Leonetti M.
Published: July 2023

Many human neural or neurodegenerative diseases strongly affect the ocular and retinal environment showing peculiar alterations which can be employed as specific disease biomarkers. The noninvasive optical accessibility of the retina makes the ocular investigation a potentially competitive strategy for screening, thus the development of retinal biomarkers is rapidly growing. Nevertheless, a tool to study and image biomarkers or biological samples in a human-like eye environment is still missing. Here we report on a modular and versatile eye model designed to host biological samples, such as retinal cultures differentiated from human induced pluripotent stem cells and ex-vivo retinal tissue, but also suited to host any kind of retinal biomarkers. We characterized the imaging performance of this eye model on standard biomarkers such as Alexa Fluor 532 and Alexa Fluor 594.