bluuebunny/crossref_metadata_2025 huggingface dataset:
Is terrorism necessarily violent? Public perceptions of nonviolence and terrorism in conflict settings
Authors: Ben Sasson-Gordis Avishay , Yakter Alon
Published: June 2023

Discussions of terrorism assume actual or threatened violence, but the term is regularly used to delegitimize rivals' nonviolent actions. Yet do ordinary citizens accept descriptions of nonviolence as terrorism? Using a preregistered survey-experiment in Israel, a salient conflictual context with diverse repertoires of contention, we find that audiences rate adversary nonviolence close to terrorism, consider it illegitimate, and justify its forceful repression. These perceptions vary by the action's threatened harm, its salience, and respondents' ideology. Explicitly labeling nonviolence as terrorism, moreover, particularly sways middle-of-the-road centrists. These relationships replicate in a lower-salience conflict, albeit with milder absolute judgments, indicating generalizability. Hence, popular perceptions of terrorism are more fluid and manipulable than assumed, potentially undermining the positive effects associated with nonviolent campaigns.
How Local Factions Pressure Parties: Activist Groups and Primary Contests in the Tea Party Era
Authors: Blum Rachel M. , Cowburn Mike
Published: June 2023

The contemporary Republican Party has been the site of asymmetric partisan entrenchment and factional infighting. We test whether factional pressure from a far-right faction (the Tea Party) exacerbated the party's rightward movement with a granular analysis of Republican factionalism at the congressional district level. We develop a measure of local factionalism using novel datasets of activist presence and primary contests. Then, we conduct a difference-in-differences analysis to assess whether local factionalism in the Tea Party era heightened Republican partisanship and legislative extremism at the district level. We find that districts that experienced factional pressure moved rightward on both measures. These findings help clarify how the Tea Party captured the Republican Party and support a focus on the role of party factions in fomenting partisan conflict.
Surgeries on iterated torus knots bounding rational homology 4-balls
Authors: Lokteva Lisa
Published: June 2023

We show that all large enough positive integral surgeries on algebraic knots bound a 4-manifold with a negative definite plumbing tree, which we describe explicitly. Then we apply the lattice embedding obstruction coming from Donaldson’s Theorem to classify the ones of the form $S^3_n(T(p_1,k_1p_1+1; p_2, k_2p_2\pm 1))$ that also bound rational homology 4-balls.
Bilateral simultaneous presentation of posterior canal benign paroxysmal positional vertigo
Authors: Yetiser Sertac , Ince Dilay
Published: June 2023

Objective

To outline the clinical picture of bilateral posterior canal benign paroxysmal positional vertigo.

Methods

A total of 573 patients with posterior canal benign paroxysmal positional vertigo were classified as having unilateral, or true or pseudo bilateral, posterior canal benign paroxysmal positional vertigo, and were treated with the Epley manoeuvre. Statistical significance was set at p < 0.05.

Results

Of the patients, 483 had unilateral and 90 (15.7 per cent) had bilateral presentation. Of the latter, 72 patients had pseudo bilateral posterior canal benign paroxysmal positional vertigo. Comparisons of site of involvement, male to female ratio and the incidence of associated problems in unilateral, and true and pseudo bilateral posterior canal benign paroxysmal positional vertigo did not reveal any statistically significant differences (p = 0.828, p = 0.200, p = 0.142). Comparisons of the number of manoeuvres required to provide symptom relief and the rate of recurrence were significant (p < 0.05).

Conclusion

Identification of true and pseudo bilateral posterior canal benign paroxysmal positional vertigo is important given the differences in aetiology and treatment outcome. Treatment of patients with true bilateral posterior canal benign paroxysmal positional vertigo requires several therapeutic manoeuvre attempts, and patients should be warned about recurrence.
Centrifugal instability in a weakly magnetized rotating plasma column
Authors: Aggarwal S. , Camenen Y. , Escarguel A. , Poyé A.
Published: June 2023

A two-fluid model is developed to study the stability of weakly magnetized rotating plasma columns. Previous works have shown that rotating plasma columns are prone to centrifugal flute modes. Most of these models are based on the low-frequency assumption which is valid when the instability frequency and the plasma azimuthal frequency are small compared with the ion cyclotron frequency. This assumption is challenged in many laboratory plasma devices, including weakly magnetized plasma columns. A radially global dispersion relation relaxing the low-frequency approximation and applicable in these devices is derived. The validity domain of the low-frequency approximation is discussed. In addition, the impact of the radial boundary on the linear stability is investigated and comparison with results obtained in the radially local approximation are performed.
Was the Habsburg Empire an Empire?
Authors: Connelly John
Published: June 2023

The Habsburg monarchy seems doubly confounding. Its historians call it an empire, but it actually never called itself that. For a fraction of its existence (1804–67), the monarchy counted as a Kaisertum, a word meant to burnish the fading glory of a lost imperial title (of the Holy Roman Empire). But its rulers never evinced the self-confident imperial aggressiveness or the desire to exploit distant territories that characterized British or Russian counterparts, and students of global empires often do not think the Habsburgs fit the category. But after calling the double monarchy an empire, Central European specialists lose the critical edge historians apply to other empires, and celebrate the Habsburgs for holding back nationalism, the force that made the twentieth century so deadly. The monarchy was not only an empire but a virtuous empire. This Kann Memorial Lecture examines a range of theoretical and practical reasons for calling the Habsburg state an empire—as its subjects often did. But if we do, we should recognize that like other empires it abhorred democracy. Perhaps more than a dam holding back the twentieth century and all its evils, the Habsburg Empire was more a conduit.
Spatiotemporal evaluation of waning grassland habitats for swamp deer conservation across the human-dominated upper Gangetic Plains, India
Authors: Paul Shrutarshi , Saha Sohini , Nigam Parag , Ali Sk Zeeshan , Page Navendu , Khan Aamer Sohel , Kumar Mukesh , Habib Bilal , Mohan Dhananjai , Pandav Bivash , Mondol Samrat
Published: June 2023

Grassland habitats currently face severe anthropogenic exploitation, thereby affecting the survival of grassland-dependent biodiversity globally. The biodiversity-rich grasslands of India lack quantitative spatiotemporal information on their status. We evaluated the status of upper Gangetic Plains grasslands in 2015 and compared it with those from 1985, 1995 and 2005. On-ground mapping and visual classifications revealed a 57% decline in these grasslands between 1985 (418 km2) and 2015 (178 km2), mostly driven by habitat conversion (74% contribution by cropland). Limited radiotelemetry data from endemic swamp deer indicated a possible grassland-dominated average home range size of 1.02 km2, and these patches were highly preferred (average Ivlev’s index = 0.85) over other land-use classes at both spatial and temporal scales. Camera-trapping within the core habitats suggests the critical use of these patches as fawning/breeding grounds. Habitat suitability analysis indicates only c. 17% of the area along the Ganges is suitable as swamp deer habitat. We recommend the protection of these critical grassland patches to maintain ‘dynamic corridors’, with restoration and other management approaches involving multiple stakeholders to ensure the survival of this critical ecosystem.
Univalent categories of modules
Authors: Flaten Jarl G. Taxerås
Published: June 2023

We show that categories of modules over a ring in homotopy type theory (HoTT) satisfy the internal versions of the AB axioms from homological algebra. The main subtlety lies in proving AB4, which is that coproducts indexed by arbitrary sets are left-exact. To prove this, we replace a set X with the strict category of lists of elements in X. From showing that the latter is filtered, we deduce left-exactness of the coproduct. More generally, we show that exactness of filtered colimits (AB5) implies AB4 for any abelian category in HoTT. Our approach is heavily inspired by Roswitha Harting’s construction of the internal coproduct of abelian groups in an elementary topos with a natural numbers object. To state the AB axioms, we define and study filtered (and sifted) precategories in HoTT. A key result needed is that filtered colimits commute with finite limits of sets. This is a familiar classical result but has not previously been checked in our setting. Finally, we interpret our most central results into an
$\infty$
-topos
$ {\mathscr{X}} $
. Given a ring R in
$ {\tau_{\leq 0}({{\mathscr{X}}})} $
– for example, an ordinary sheaf of rings – we show that the internal category of R-modules in
$ {\mathscr{X}} $
represents the presheaf which sends an object
$ X \in {\mathscr{X}} $
to the category of
$ (X{\times}R) $
-modules in
${\mathscr{X}} / X$
. In general, our results yield a product-preserving left adjoint to base change of modules over X. When X is 0-truncated, this left adjoint is the internal coproduct. By an internalisation procedure, we deduce left-exactness of the internal coproduct as an ordinary functor from its internal left-exactness coming from HoTT.
Negotiating Dissonance between the Religious, the Civil and the Legal in Anglican Same-Sex Weddings
Authors: Bethmont Rémy
Published: June 2023

With the adoption of same-sex marriage or marriage-like schemes by civil authorities on both sides of the North Atlantic, Anglican same-sex couples in England, Scotland and the United States have had to negotiate various forms of dissonance between the religious celebration and the legal or civil status of their unions. This often translates into couples having multiple celebrations of their unions in order to bring together the legal and the religious creatively. These multiple ceremonies evidence the grip exercised by the tradition of a single wedding ritual that is both religious and legal on the imagination of Anglican same-sex couples. Enduring attachment to this tradition has given rise to particular LGBTQ ways of relating the celebration of a union to time, thus contributing to the unravelling of a rigidly legal Anglican understanding of the marriage rite.
The Renunciation of Wealth as a Rite of ‘the poor' and ‘perfect’: Bede and his Successors
Authors: Guiliano Zachary
Published: June 2023

The renunciation and abandonment of wealth are rarely described as Christian rites of passage. Yet, for many medieval commentators on Scripture, such as the Venerable Bede and his successors, they were necessary rites, preliminaries to entry into the kingdom of heaven and into the class of ‘the perfect’. This article explores Arnold van Gennep's description of rites of passage in conjunction with the discussion of poverty in the Western exegetical tradition, centred in particular on Jesus's statements about poverty in Luke. It focuses on Bede's models of renunciation and abandonment of wealth which influenced Latin theology at least until the Reformation. The renunciation and abandonment of wealth provide an excellent test case for exploring van Gennep's ritual framework and its utility within the discipline of ecclesiastical history.
The Blessing of the Wedding Bedchamber in North-Western Europe, c.950–c.1200
Authors: van Houts Elisabeth
Published: June 2023

This article addresses two specific problems. First, between c.950 and c.1200 there appears to be a mismatch between liturgical manuscripts and narrative sources on the Christian blessing of the wedding bedchamber and bed, with the former recording the ritual but the latter scarcely mentioning it. The second concerns the question as to whether the ritual was expected to take place at home or in the church. In order to shed light on the development of the ritual, where it took place and how frequently, the article is divided into four parts. A discussion of liturgical manuscripts for the blessing of the wedding bedchamber and bed is followed by an analysis of the prayers to establish why the wedding bedchamber and the bed warranted a blessing. We then turn to an evaluation of the sparse evidence for the priest's liturgical role at home weddings. Finally, the liturgical evidence is linked to historical and fictional evidence. The article concludes that ambiguity about where the ritual should take place allowed for discretion on the part of those involved, and that the great majority of the laity may have been ignorant of the ritual altogether.
‘The Child's blood should lye at his Door’: Local Divisions over Baptismal Rites during the English Civil War and the Interregnum
Authors: McCall Fiona
Published: June 2023

By the 1640s, Prayer Book ritual had marked rites of passage in England for over eighty years. It formed a reassuring continuum with older Catholic rites and gave communality to parish religion. However, puritans disliked its ceremonial elements, which were banned by Parliament in the 1640s. Anecdotal evidence suggests that parishioners continued to demand old-style rites of passage, and some clergy to offer them. This has led historians to suggest that traditionalist practice was condoned by the regime. This article uses loyalist memories of antagonisms between puritan and non-puritan clergy and parishioners over baptism, as well as evidence from legal prosecutions and other sources, to complicate such presumptions, showing how, with opinion sharply divided on their practice, rites of passage led to clashes and confrontations within parishes and remained a focus for local antagonism.
Die Bedeutung frühkindlicher Schlafprobleme für das spätere familiale Wohlergehen
Authors: Lux Ulrike , Friedmann Anna
Published: June 2023

Zusammenfassung: Theoretischer Hintergrund: Die längerfristige Bedeutung kindlicher Schlafprobleme für die gesamte Familie ist kaum erforscht. Fragestellung: (1) Sind kindliche Schlafprobleme prädiktiv für das familiale Wohlergehen auf Elternebene, Eltern-Kind-Beziehungsebene und die kindliche negative Emotionalität zwei Jahre später? (2) Ist die frühere korrespondierende elterliche Belastung ein Mediator? Methode: Die Längsschnittstudie von N = 669 Familien (T2: MAlter Elternteil = 36.93 Jahre, SD = 4.95; 7.0 % Väter) mit Kleinkindern (T2: M= 39.62 Monate, SD = 11.28; 49.5 % Mädchen) untersuchte die Folgen elternberichteter frühkindlicher Schlafprobleme und der korrespondierenden elterlichen Belastung für das familiale Wohlergehen (z. B. Angst- und Depressionssymptome, elterliche Kompetenzzweifel) sowie für die kindliche negative Emotionalität zu T1 und T2 mithilfe eines Mediationsmodells. Ergebnisse: Schlafprobleme zu T1 prädizieren das Wohlergehen auf Eltern- und Eltern-Kind-Beziehungsebene zu T2, vollständig mediiert über die frühere elterliche Belastung. Diskussion und Schlussfolgerung: Kindliche Schlafprobleme sind noch zwei Jahre später für das Wohlergehen auf Eltern- und Eltern-Kind-Beziehungsebene über die elterliche Belastung bedeutsam. Beeinträchtigungen des elterlichen Wohlergehens und der Eltern-Kind-Beziehung sollten bei Diagnostik und Therapie noch stärker berücksichtigt werden.
Optimizing Simultaneous Water Level and Wave Measurements From Multi‐GNSS Interferometric Reflectometry Over 1 Year at an Exposed Coastal Site
Authors: Sepúlveda Ignacio , Cao Bing , Haase Jennifer S. , Murphy Michael J.
Published: June 2023

Global Navigation Satellite System Interferometric Reflectometry (GNSS‐IR) measures water level using the interference pattern in signal‐to‐noise ratio (SNR) from direct and reflected signals off the sea surface, retrieved from standard geodetic antennas. Significant wave height is also measured by determining the satellite elevation angles where reflections become incoherent. We developed an approach for standard geodetic antennas to simultaneously measure sea levels and waves using a criterion for identifying coherent reflections. We tested the method at an exposed coastal environment at the E.B. Scripps Memorial Pier in California. The 1‐year test captures a broad range of sea states and benefits from several co‐located standard oceanographic sensors. By including GPS, Galileo, and GLONASS observations, the retrieval rate increases by a factor of ∼2 over GPS alone. Uncorrected water levels are estimated with a root‐mean‐square (RMS) error of 18.2 cm with respect to a conventional tide gauge. We further developed a simplified correction to remove the effect of phenomena altering the SNR oscillatory frequency and phase, which reduces RMS errors to 9.4 cm. We estimate the significant wave height with 15 cm RMS error with respect to a traditional wave gauge. The method, however, requires a short calibration. We find the wave height errors increase abruptly beyond a fixed limit when high waves are present, that may be a result of the particular deployment geometry. With this caveat, the technology could be useful to deploy in under‐sampled regions affected by compounded coastal hazards, such as in areas affected by tropical cyclones and flooding.
The Flocculation State of Mud in the Lowermost Freshwater Reaches of the Mississippi River: Spatial Distribution of Sizes, Seasonal Changes, and Their Impact on Vertical Concentration Profiles
Authors: Osborn Ryan , Dunne Kieran B. J. , Ashley Thomas , Nittrouer Jeffrey A. , Strom Kyle
Published: June 2023

We use in situ measurements of suspended mud to assess the flocculation state of the lowermost freshwater reaches of the Mississippi River. The goal of the study was to assess the flocculation state of the mud in the absence of seawater, the spatial distribution of floc sizes within the river, and to look for seasonal differences between summer and winter. We also examine whether measured floc sizes can explain observed vertical distributions of mud concentration through a Rouse profile analysis. Data were collected at the same locations during summer and winter at similar discharges and suspended sediment concentrations. Measurements showed that the mud in both seasons was flocculated and that the floc size could reasonably be represented by a cross‐sectional averaged value as sizes varied little over the flow depth or laterally across the river at a given station. Depth‐averaged floc sizes ranged from 75 to 200 microns and increased slightly moving downriver as turbulence levels dropped. On average, flocs were 40 microns larger during summer than in winter, likely due to enhanced microbial activity associated with warmer water. Floc size appeared to explain vertical variations in mud concentration profiles when the bed was predominately composed of sand. Average mud settling velocities for these cases ranged from 0.1 to 0.5 mm/s. However, Rouse‐estimated settling velocities ranged from 1 to 3 mm/s at two stations during winter where the bed was composed of homogeneous mud. These values exceeded the size‐based estimates of settling velocity.
Developmental manifestations of polygenic risk for bipolar disorder from infancy to middle childhood
Authors: Askeland Ragna Bugge , Hannigan Laurie J. , O’Connell Kevin S. , Corfield Elizabeth C. , Frei Oleksandr , Thapar Anita , Smith George Davey , Reichborn-Kjennerud Ted , Andreassen Ole A. , Ask Helga , Havdahl Alexandra
Published: June 2023

Knowledge on how genetic risk for bipolar disorder manifests in developmental, emotional or behavioral traits during childhood is lacking. This issue is important to address to inform early detection and intervention efforts. We investigated whether polygenic risk for bipolar disorder is associated with developmental outcomes during early to middle childhood in the general population, and if associations differ between boys and girls. Our sample consisted of 28 001 children from the Norwegian Mother, Father and Child Cohort study, a prospective pregnancy cohort with available genotype and developmental data. Mothers reported on a range of developmental outcomes in their children at 6 and 18 months, 3, 5 and 8 years. Polygenic risk scores reflecting common variant liability to bipolar disorder were calculated. Linear regression models were used in a multi-group framework to investigate associations between polygenic risk score and developmental outcomes, using sex as a grouping variable. We found robust evidence for an association between polygenic risk scores for bipolar disorder and conduct difficulties (β = 0.041, CI = 0.020–0.062) and oppositional defiant difficulties (β = 0.032, CI = 0.014–0.051) at 8 years. Associations with most other outcomes were estimated within the region of practical equivalence to zero (equivalence range D = −0.1 to 0.1), with the exceptions of negative association for activity levels (β = −0.028, CI = −0.047– −0.010) at age 5 and benevolence (β = −0.025, CI = –0.043 to –0.008) at age 8, and positive association for motor difficulties (β = 0.025, CI = 0.008–0.043) at age 3, inattention (β = 0.021, CI = 0.003–0.041) and hyperactivity (β = 0.025, CI = 0.006–0.044) at age 8. Our results suggest that genetic risk for bipolar disorder manifests as disruptive behaviors like oppositional defiant and conduct difficulties in childhood in the general population.
Associated medical conditions among 10-year-old children with oral clefts - a retrospective review across three cleft centres: Part 2
Authors: Gee Samantha , Ezzeldin Maryam , Curtis Jacob , Clark Victoria J. , Smallridge Jacqueline , Collard Mechelle
Published: June 2023

IntroductionIn many cases, children with oral clefts present with accompanying medical conditions. These associated conditions can add complexity to the patient's dental management, both in terms of their treatment need and risk. Recognition and careful consideration of associated medical conditions is therefore crucial in providing safe and effective care for these patients.

AimThis paper is the second in a two-part three-centre series. It investigates the prevalence of medical conditions affecting cleft lip and/or palate patients attending three cleft units within the UK.

MethodRetrospective review was undertaken within three cleft units: South Wales (SW), Cleft NET East (CNE) and West Midlands (WM). This was completed via assessment of the 10-year audit record appointment clinical notes for the year 2016/2017.

ResultsIn total, 144 cases were reviewed (SW = 42; CNE = 52; WM = 50). Of these, 38.9% of patients (n = 56) had associated medical conditions recorded.

DiscussionThe review highlights the variety and impact of medical conditions affecting UK cleft patients providing insight into the consequent complexity of their dental care.

ConclusionAn awareness of cleft lip and/or palate patients' associated medical conditions is important for all health care professionals involved in their care. Indeed, understanding of the patient's medical needs by multidisciplinary cleft teams is essential for effective planning and completion of holistic care. Involvement of specialists in paediatric dentistry sharing care with general dental practitioners is vital in providing appropriate oral health care and preventive support.
Role of liensinine in sensitivity of activated macrophages to ferroptosis and in acute liver injury
Authors: Li Jing , Huang Qi , Lv Minling , Ma Wenfeng , Sun Jialing , Zhong Xin , Hu Rui , Ma MengQing , Han Zhiyi , Zhang Wei , Feng Wenxing , Sun Xinfeng , Zhou Xiaozhou
Published: June 2023

Acute liver injury (ALI) is an acute inflammatory liver disease with a high mortality rate. Alternatively, activated macrophages (AAMs) have been linked to the inflammation and recovery of ALI. However, the mechanism underlying AAM death in ALI has not been studied sufficiently. We used liensinine (Lie) as a drug of choice after screening a library of small-molecule monomers with 1488 compounds from traditional Chinese remedies. In ALI, we evaluated the potential therapeutic effects and underlying mechanisms of action of the drug in ALI and found that it effectively inhibited RSL3-induced ferroptosis in AAM. Lie significantly reduced lipid peroxidation in RSL3-generated AAM. It also improved the survival rate of LPS/D-GalN-treated mice, reduced serum transaminase activity, suppressed inflammatory factor production, and may have lowered AAM ferroptosis in ALI. Lie also inhibited ferritinophagy and blocked Fe2+ synthesis. Following combined treatment with RSL3 and Lie, super-resolution microscopy revealed a close correlation between ferritin and LC3-positive vesicles in the AAM. The co-localization of ferritin and LC3 with LAMP1 was significantly reduced. These findings suggest that Lie may ameliorate ALI by inhibiting ferritinophagy and enhancing AMM resistance to ferroptosis by inhibiting autophagosome-lysosome fusion. Therefore, Lie may be used as a potential therapeutic agent for patients with ALI.
Modular assembly of metal nanoparticles/mesoporous carbon two-dimensional nanosheets
Authors: Qiu Pengpeng , Zhang Xingmiao , Ai Yan , Luo Wei , Li Wei , Zhao Dongyuan
Published: June 2023

The manipulation of polymeric micelles across extended-length scales is a key challenge in the design of integrated mesoporous materials with well-defined geometry and advanced functions. Herein, we demonstrate a modular assembly strategy to construct metal nanoparticle functionalized mesoporous carbon two-dimensional (2D) nanosheets by organizing zero-dimensional (0D) spherical monomicelle modules on the 2D supporting blocks. The modular assembly process involves two key steps: the “modularization” step is used to synthesize highly uniform metal–catecholamine (MC) complex functionalized monomicelle “modules” that can be conveniently assembled on the 2D supporting blocks (graphene oxide (GO), WS2, and MXene) in the following “assembly” step. After an annealing process, the resultant composites possess a single-layered 2D nanosheet surrounded by two single-layered mesoporous carbon at both sides and exhibit highly ordered mesostructures with large surface areas (~385 m2 g−1), tunable pore sizes (16–25 nm) and highly dispersed metal-containing nanoparticles. Due to the modularity of this assembly process, a range of metal species (Co, Fe, Ni, V, Cu, Pd, FeCo, CoNi, and FeCoNi) can be in-situ incorporated into the 2D mesoporous frameworks, which are partially embedded in the pore walls with the remaining part exposed in the pore channels. Benefiting from the unique textual structures, the resultant GO-derived functional mesoporous carbon nanosheets (Co as the functional species and being annealed at 850 °C) exhibit excellent electrocatalytic activity, long-term stability, and superior methanol tolerance for oxygen reduction reaction, which holds great potential as a catalyst for fuel cells.
Enhanced radiosensitivity and chemoradiation efficacy in nasopharyngeal carcinoma via a dual-targeted SPION@polymer hybrid nanosensitizer
Authors: Ding Yuxun , Xiao Xiaohui , Bai Lu , Yang Bowen , Lin Guanghui , Zeng Lingli , Xie Lisi , Li Lei , Duan Xiaohui , Shen Jun , Zhou Jianhua , Pan Yue
Published: June 2023

Cisplatin-based nanoparticles show good potential in enhancing the effect of nasopharynx carcinoma (NPC) therapy but are still limited by their low radiation sensitization and poor tumor targeting ability. Herein, an ingenious design of multifunctional superparamagnetic iron oxide nanoparticle (SPION)@polymer hybrid nanosensitizer (SPHN) with enhanced radiosensitization and dual-targeting capability is described. SPHN have a core-shell structure, in which radiosensitizer superparamagnetic iron oxide particle (SPION) and cis-platinum (CDDP) are encapsulated in RGD-conjugated amphiphilic block copolymers. These unique structures endow SPHN with outstanding radiosensitization and tumor targeting abilities. When combined with X-rays, SPHN showed strong promotion of the apoptosis of CNE-1 cells in vitro. In addition, RNA-seq and KEGG enrichment analyses indicated that the PI3K-Akt and TNF signaling pathways were closely related to the molecular mechanism of SPHN in chemoradiotherapy. Furthermore, gene set enrichment analysis (GSEA) revealed that SPHN + X-rays treatment decreased translation initiation pathways and the cytoplasmic translation pathway. Through a combination of radiation and chemotherapy, SPHN can achieve remarkable inhibition of tumor growth in vivo, making this nanotechnology a general platform for the chemoradiation therapy of NPC in the future.
Development of electroresponsive functional soft materials by electroresponsive dopants
Authors: Itoh Yoshimitsu , Morishita Daiki
Published: June 2023

In this Focus Review, we summarize our new strategy to create electroresponsive soft materials using electroresponsive dopants. Liquid crystals (LCs) are representative electroresponsive soft functional materials that have been utilized for various applications, including LC display devices. The response to the applied electric field (E-field) is generally realized by the direct coupling between the E-field and the LC molecules. Thus, LC molecules must simultaneously exhibit electroresponsiveness and LC properties. As a new concept to create electroresponsive soft materials, we came up with an idea of using electroresponsive dopants. Dopants can change the property of the LC material only with a minute amount and do not need to have an LC property by itself, thus allows more freedom for the molecular design. Based on this new concept, we developed several intriguing materials, such as cholesteric displays with rewritable color memory functions and quick color modulation functions, which are both unprecedented. We also utilized this concept to columnar LC systems and realized multiresponsive columnar LC materials, which are usually rigid and poorly responsive to applied external perturbations.
Eagle eyed or bird brained?
Authors: Williams David
Published: June 2023

The importance of the visual system to birds for behaviours from feeding, mate choice, flying, navigation and determination of seasons, together with the presence of photoreceptors in the retina, the pineal and the brain, render the avian visual system a particularly fruitful model for understanding of eye-brain interactions. In this review we will particularly focus on the pigeon, since here we have a brain stereotactically mapped and a genome fully sequenced, together with a particular bird, the homing pigeon, with remarkable ability to navigate over hundreds of miles and return to exactly the same roosting site with exceptional precision. We might denigrate the avian species by the term bird brained, but here are animals with phenomenal abilities to use their exceptional vision, their eagle eyedness, to best advantage.
The role of mechano-regulated YAP/TAZ in erectile dysfunction
Authors: Ji Mintao , Chen Dongsheng , Shu Yinyin , Dong Shuai , Zhang Zhisen , Zheng Haimeng , Jin Xiaoni , Zheng Lijun , Liu Yang , Zheng Yifei , Zhang Wensheng , Wang Shiyou , Zhou Guangming , Li Bingyan , Ji Baohua , Yang Yong , Xu Yongde , Chang Lei
Published: June 2023

Phosphodiesterase type 5 inhibitors (PDE5is) constitute the primary therapeutic option for treating erectile dysfunction (ED). Nevertheless, a substantial proportion of patients, approximately 30%, do not respond to PDE5i treatment. Therefore, new treatment methods are needed. In this study, we identified a pathway that contributes to male erectile function. We show that mechano-regulated YAP/TAZ signaling in smooth muscle cells (SMCs) upregulates adrenomedullin transcription, which relaxed the SMCs to maintain erection. Using single-nucleus RNA sequencing, we investigated how penile erection stretches the SMCs, inducing YAP/TAZ activity. Subsequently, we demonstrate that YAP/TAZ plays a role in erectile function and penile rehabilitation, using genetic lesions and various animal models. This mechanism relies on direct transcriptional regulation of adrenomedullin by YAP/TAZ, which in turn modulates penile smooth muscle contraction. Importantly, conventional PDE5i, which targets NO-cGMP signaling, does not promote erectile function in YAP/TAZ-deficient ED model mice. In contrast, by activating the YAP/TAZ-adrenomedullin cascade, mechanostimulation improves erectile function in PDE5i nonrespondent ED model rats and mice. Furthermore, using clinical retrospective observational data, we found that mechanostimulation significantly promotes erectile function in patients irrespective of PDE5i use. Our studies lay the groundwork for exploring the mechano-YAP/TAZ-adrenomedullin axis as a potential target in the treatment of ED.
Systems-level analyses of protein-protein interaction network dysfunctions via epichaperomics identify cancer-specific mechanisms of stress adaptation
Authors: Rodina Anna , Xu Chao , Digwal Chander S. , Joshi Suhasini , Patel Yogita , Santhaseela Anand R. , Bay Sadik , Merugu Swathi , Alam Aftab , Yan Pengrong , Yang Chenghua , Roychowdhury Tanaya , Panchal Palak , Shrestha Liza , Kang Yanlong , Sharma Sahil , Almodovar Justina , Corben Adriana , Alpaugh Mary L. , Modi Shanu , Guzman Monica L. , Fei Teng , Taldone Tony , Ginsberg Stephen D. , Erdjument-Bromage Hediye , Neubert Thomas A. , Manova-Todorova Katia , Tsou Meng-Fu Bryan , Young Jason C. , Wang Tai , Chiosis Gabriela
Published: June 2023

Systems-level assessments of protein-protein interaction (PPI) network dysfunctions are currently out-of-reach because approaches enabling proteome-wide identification, analysis, and modulation of context-specific PPI changes in native (unengineered) cells and tissues are lacking. Herein, we take advantage of chemical binders of maladaptive scaffolding structures termed epichaperomes and develop an epichaperome-based ‘omics platform, epichaperomics, to identify PPI alterations in disease. We provide multiple lines of evidence, at both biochemical and functional levels, demonstrating the importance of these probes to identify and study PPI network dysfunctions and provide mechanistically and therapeutically relevant proteome-wide insights. As proof-of-principle, we derive systems-level insight into PPI dysfunctions of cancer cells which enabled the discovery of a context-dependent mechanism by which cancer cells enhance the fitness of mitotic protein networks. Importantly, our systems levels analyses support the use of epichaperome chemical binders as therapeutic strategies aimed at normalizing PPI networks.
TRPV4-Rho GTPase complex structures reveal mechanisms of gating and disease
Authors: Kwon Do Hoon , Zhang Feng , McCray Brett A. , Feng Shasha , Kumar Meha , Sullivan Jeremy M. , Im Wonpil , Sumner Charlotte J. , Lee Seok-Yong
Published: June 2023

Crosstalk between ion channels and small GTPases is critical during homeostasis and disease, but little is known about the structural underpinnings of these interactions. TRPV4 is a polymodal, calcium-permeable cation channel that has emerged as a potential therapeutic target in multiple conditions. Gain-of-function mutations also cause hereditary neuromuscular disease. Here, we present cryo-EM structures of human TRPV4 in complex with RhoA in the ligand-free, antagonist-bound closed, and agonist-bound open states. These structures reveal the mechanism of ligand-dependent TRPV4 gating. Channel activation is associated with rigid-body rotation of the intracellular ankyrin repeat domain, but state-dependent interaction with membrane-anchored RhoA constrains this movement. Notably, many residues at the TRPV4-RhoA interface are mutated in disease and perturbing this interface by introducing mutations into either TRPV4 or RhoA increases TRPV4 channel activity. Together, these results suggest that RhoA serves as an auxiliary subunit for TRPV4, regulating TRPV4-mediated calcium homeostasis and disruption of TRPV4-RhoA interactions can lead to TRPV4-related neuromuscular disease. These insights will help facilitate TRPV4 therapeutics development.
Targeting neddylation sensitizes colorectal cancer to topoisomerase I inhibitors by inactivating the DCAF13-CRL4 ubiquitin ligase complex
Authors: Sun Yilun , Baechler Simone A. , Zhang Xiaohu , Kumar Suresh , Factor Valentina M. , Arakawa Yasuhiro , Chau Cindy H. , Okamoto Kanako , Parikh Anup , Walker Bob , Su Yijun P. , Chen Jiji , Ting Tabitha , Huang Shar-yin N. , Beck Erin , Itkin Zina , McKnight Crystal , Xie Changqing , Roper Nitin , Nijhawan Deepak , Figg William Douglas , Meltzer Paul S. , Yang James C. , Thomas Craig J. , Pommier Yves
Published: June 2023

Colorectal cancers (CRCs) are prevalent worldwide, yet current treatments remain inadequate. Using chemical genetic screens, we identify that co-inhibition of topoisomerase I (TOP1) and NEDD8 is synergistically cytotoxic in human CRC cells. Combination of the TOP1 inhibitor irinotecan or its bioactive metabolite SN38 with the NEDD8-activating enzyme inhibitor pevonedistat exhibits synergy in CRC patient-derived organoids and xenografts. Mechanistically, we show that pevonedistat blocks the ubiquitin/proteasome-dependent repair of TOP1 DNA-protein crosslinks (TOP1-DPCs) induced by TOP1 inhibitors and that the CUL4-RBX1 complex (CRL4) is a prominent ubiquitin ligase acting on TOP1-DPCs for proteasomal degradation upon auto-NEDD8 modification during replication. We identify DCAF13, a DDB1 and Cullin Associated Factor, as the receptor of TOP1-DPCs for CRL4. Our study not only uncovers a replication-coupled ubiquitin-proteasome pathway for the repair of TOP1-DPCs but also provides molecular and translational rationale for combining TOP1 inhibitors and pevonedistat for CRC and other types of cancers.
A reconfigurable binary/ternary logic conversion-in-memory based on drain-aligned floating-gate heterojunction transistors
Authors: Lee Chungryeol , Lee Changhyeon , Lee Seungmin , Choi Junhwan , Yoo Hocheon , Im Sung Gap
Published: June 2023

A new type of heterojunction non-volatile memory transistor (H-MTR) has been developed, in which the negative transconductance (NTC) characteristics can be controlled systematically by a drain-aligned floating gate. In the H-MTR, a reliable transition between N-shaped transfer curves with distinct NTC and monolithically current-increasing transfer curves without apparent NTC can be accomplished through programming operation. Based on the H-MTR, a binary/ternary reconfigurable logic inverter (R-inverter) has been successfully implemented, which showed an unprecedentedly high static noise margin of 85% for binary logic operation and 59% for ternary logic operation, as well as long-term stability and outstanding cycle endurance. Furthermore, a ternary/binary dynamic logic conversion-in-memory has been demonstrated using a serially-connected R-inverter chain. The ternary/binary dynamic logic conversion-in-memory could generate three different output logic sequences for the same input signal in three logic levels, which is a new logic computing method that has never been presented before.
Light-driven self-assembly of spiropyran-functionalized covalent organic framework
Authors: Das Gobinda , Prakasam Thirumurugan , Alkhatib Nour , AbdulHalim Rasha G. , Chandra Falguni , Sharma Sudhir Kumar , Garai Bikash , Varghese Sabu , Addicoat Matthew A. , Ravaux Florent , Pasricha Renu , Jagannathan Ramesh , Saleh Na’il , Kirmizialtin Serdal , Olson Mark A. , Trabolsi Ali
Published: June 2023

Controlling the number of molecular switches and their relative positioning within porous materials is critical to their functionality and properties. The proximity of many molecular switches to one another can hinder or completely suppress their response. Herein, a synthetic strategy involving mixed linkers is used to control the distribution of spiropyran-functionalized linkers in a covalent organic framework (COF). The COF contains a spiropyran in each pore which exhibits excellent reversible photoswitching behavior to its merocyanine form in the solid state in response to UV/Vis light. The spiro-COF possesses an urchin-shaped morphology and exhibits a morphological transition to 2D nanosheets and vesicles in solution upon UV light irradiation. The merocyanine-equipped COFs are extremely stable and possess a more ordered structure with enhanced photoluminescence. This approach to modulating structural isomerization in the solid state is used to develop inkless printing media, while the photomediated polarity change is used for water harvesting applications.
Ordering of room-temperature magnetic skyrmions in a polar van der Waals magnet
Authors: Meisenheimer Peter , Zhang Hongrui , Raftrey David , Chen Xiang , Shao Yu-Tsun , Chan Ying-Ting , Yalisove Reed , Chen Rui , Yao Jie , Scott Mary C. , Wu Weida , Muller David A. , Fischer Peter , Birgeneau Robert J. , Ramesh Ramamoorthy
Published: June 2023

Control and understanding of ensembles of skyrmions is important for realization of future technologies. In particular, the order-disorder transition associated with the 2D lattice of magnetic skyrmions can have significant implications for transport and other dynamic functionalities. To date, skyrmion ensembles have been primarily studied in bulk crystals, or as isolated skyrmions in thin film devices. Here, we investigate the condensation of the skyrmion phase at room temperature and zero field in a polar, van der Waals magnet. We demonstrate that we can engineer an ordered skyrmion crystal through structural confinement on the μm scale, showing control over this order-disorder transition on scales relevant for device applications.
Colloid driven low supersaturation crystallization for atomically thin Bismuth halide perovskite
Authors: Li Lutao , Yao Junjie , Zhu Juntong , Chen Yuan , Wang Chen , Zhou Zhicheng , Zhao Guoxiang , Zhang Sihan , Wang Ruonan , Li Jiating , Wang Xiangyi , Lu Zheng , Xiao Lingbo , Zhang Qiang , Zou Guifu
Published: June 2023

It is challenging to grow atomically thin non-van der Waals perovskite due to the strong electronic coupling between adjacent layers. Here, we present a colloid-driven low supersaturation crystallization strategy to grow atomically thin Cs3Bi2Br9. The colloid solution drives low-concentration solute in a supersaturation state, contributing to initial heterogeneous nucleation. Simultaneously, the colloids provide a stable precursor source in the low-concentration solute. The surfactant is absorbed in specific crystal nucleation facet resulting in the anisotropic growth of planar dominance. Ionic perovskite Cs3Bi2Br9 is readily grown from monolayered to six-layered Cs3Bi2Br9 corresponding to thicknesses of 0.7, 1.6, 2.7, 3.6, 4.6 and 5.7 nm. The atomically thin Cs3Bi2Br9 presents layer-dependent nonlinear optical performance and stacking-induced second harmonic generation. This work provides a concept for growing atomically thin halide perovskite with non-van der Waal structures and demonstrates potential application for atomically thin single crystals’ growth with strong electronic coupling between adjacent layers.
Practical intelligent diagnostic algorithm for wearable 12-lead ECG via self-supervised learning on large-scale dataset
Authors: Lai Jiewei , Tan Huixin , Wang Jinliang , Ji Lei , Guo Jun , Han Baoshi , Shi Yajun , Feng Qianjin , Yang Wei
Published: June 2023

Cardiovascular disease is a major global public health problem, and intelligent diagnostic approaches play an increasingly important role in the analysis of electrocardiograms (ECGs). Convenient wearable ECG devices enable the detection of transient arrhythmias and improve patient health by making it possible to seek intervention during continuous monitoring. We collected 658,486 wearable 12-lead ECGs, among which 164,538 were annotated, and the remaining 493,948 were without diagnostic. We present four data augmentation operations and a self-supervised learning classification framework that can recognize 60 ECG diagnostic terms. Our model achieves an average area under the receiver-operating characteristic curve (AUROC) and average F1 score on the offline test of 0.975 and 0.575. The average sensitivity, specificity and F1-score during the 2-month online test are 0.736, 0.954 and 0.468, respectively. This approach offers real-time intelligent diagnosis, and detects abnormal segments in long-term ECG monitoring in the clinical setting for further diagnosis by cardiologists.
An integrative mathematical model for timing treatment toxicity and Zeitgeber impact in colorectal cancer cells
Authors: Hesse Janina , Müller Tim , Relógio Angela
Published: June 2023

Increasing evidence points to a role of the circadian clock in the regulation of cancer hallmarks with a strong impact on the understanding and treatment of this disease. Anti-cancer treatment can be personalized considering treatment timing. Here we present a new mathematical model based on data from three colorectal cancer cell lines and core-clock knock-outs, which couples the circadian and drug metabolism network, and that allows to determine toxicity profiles for a given drug and cell type. Moreover, this model integrates external Zeitgebers and thus may be used to fine-tune toxicity by using external factors, such as light, and therefore, to a certain extent, help fitting the endogenous rhythms of the patients to a defined clinic routine facilitating the implementation of time-dependent treatment in clinical practice.
Medium-throughput image-based phenotypic siRNA screen to unveil the molecular basis of B cell polarization
Authors: Obino Dorian , Maurin Mathieu , Dingli Florent , Loew Damarys , Lescure Aurianne , Terriac Emmanuel , Goudot Christel , Malbec Odile , Lankar Danielle , Yuseff Maria-Isabel , Lennon-Duménil Ana-Maria , Moreau Hélène D.
Published: June 2023

Cell polarity is an essential and highly conserved process governing cell function. Cell polarization is generally triggered by an external signal that induces the relocation of the centrosome, thus defining the polarity axis of the cell. Here, we took advantage of B cells as a model to study cell polarity and perform a medium-throughput siRNA-based imaging screen to identify new molecular regulators of polarization. We first identified candidates based on a quantitative proteomic analysis of proteins differentially associated with the centrosome of resting non-polarized and stimulated polarized B cells. We then targeted 233 candidates in a siRNA screen and identified hits regulating the polarization of the centrosome and/or lysosomes in B cells upon stimulation. Our dataset of proteomics, images, and polarity indexes provides a valuable source of information for a broad community of scientists interested in the molecular mechanisms regulating cell polarity.