bluuebunny/crossref_metadata_2025 huggingface dataset:
Serial Murder and Honor: Rereading the Story of an Ottoman Murderess
Authors: Cora N. İpek Hüner
Published: March 2022

Murderesses are not among the stock characters of Ottoman prose stories, but they give us a rare opportunity to discuss how being a woman and committing a crime is represented in literary fiction. They also give us the opportunity to discuss how these stories might have been perceived by their audiences. With that in mind, I suggest a close reading of a story that I will summarize here. The story raises questions regarding narratives, gender, and honor as represented and perceived in fiction.
Crime, Gender, Sexuality: Female Villains in Late Ottoman Crime Fiction
Authors: Balsoy Gülhan
Published: March 2022

In 1914, a Turkish novella depicting a young woman pressing a dagger to the throat of a bearded old man on its cover, with the title Bloody Fairy (Kanlı Peri), appeared for sale on bookshelves in the capital of the Ottoman Empire (Fig. 1). This relatively small book of fifty-four pages, with its price as low as 50 paras, was available to almost anybody who wanted to purchase and read it. Bloody Fairy was the first of a popular series of ten murder mysteries, National Collection of Murders (Milli Cinayat Koleksiyonu), written by Süleyman Sudi and Vassaf Kadri. On the back cover of the first book, the publishers promised readers that the series would tell matchless mysterious and murderous stories that “will arouse curiosity and excitement” (merak-aver ve heyecan-amiz ) among readers. This cover image must have been rather curious since popular crime fiction usually featured male protagonists as their central characters. In those books women were almost always the target, not the ones attacking men or committing crimes. A crime story featuring a female character leading a gang, not falling victim to a male criminal or being his lover, was not a figure that readers would expect. The preface of this book—and indeed the whole series—depicts countless oddities, strange events, enigmatic murders, and other crimes that had taken place in Istanbul during the prior twenty years. Many of these events were carried out by women. The authors write that although there was nothing astonishing in crimes committed because of a woman, women committing crimes was something never seen or heard of. Thus, they surely hoped that this extraordinary crime series about two female criminals would be a commercial success. On the back cover of the first book, they announced that the series would be published as two parts, comprising ten books each, and would be offered for sale as individual titles every Thursday. Unfortunately, their grand plans were never fulfilled; only the first ten books were published. Although the series is far from complete and we will never know about the authors’ plans to unfurl further crimes and mysteries, something wondrous eventually happened: these two authors, who were never among the canon of Ottoman Turkish literature, were discovered in the 2000s. In addition to National Collection of Murders, several of their other works have been transcribed and published. Süleyman Sudi and Vassaf Kadri, who yearned for popularity in the early 20th century, indeed became popular, albeit a century late.
Betraying Behita: Superstition and the Paralysis of Blackness in Out el Kouloub's Zanouba
Authors: Moore Taylor M.
Published: March 2022

At the climax of Egyptian author Out el Kouloub's novel, Zanouba, the reader is witness to a crime. We find ourselves in Matariyya, a village north of Cairo, in a somber bedchamber with a blind shaykh. It is the room where only a week before Zanouba, the novel's titular character, suffered a forced miscarriage in the final month of her pregnancy and lost her long-coveted male child. The women of the household are lined up in front of the shaykh—all except for Zanouba, who is still bedridden, and her co-wife, Mashallah, who is exempt from participating because she is menstruating. They prepare to swear on the Qurʾan their innocence in the matter of the miscarriage, as Zanouba's husband, Abdel Meguid, and her mother-in-law suspect foul play.
Anti-Christ in Egypt: Sexual Danger, Race, and Crime in a Narrative of Imperial Crisis
Authors: Biancani Francesca
Published: March 2022

For a long time, women's crime has been quite a no-go area for feminist thinkers. With the lesser frequency of female crime seemingly encouraging quantitative-minded criminologists to dismiss a gendered approach as altogether irrelevant, theories of crime, in fact, have been mostly written by and tested on men. The emergence of a feminist perspective in criminology pluralized and decentered the disciplinary epistemology with important outcomes. On one side, it paved the way for the investigation of the distinctive ways in which individuals socialized as women commit crimes, deconstructing the die-hard stereotype of female criminals’ abnormality, that is, the idea that female offenders deviate from a female standard of nondelinquency. On the other, quoting Loraine Gelsthorpe, feminist criminology “has not only developed a critique of accumulated wisdom about female offenders and victims, but has illuminated institutionalized sexism within criminological theory, policy and practice.” Feminism has stimulated the production of criminological knowledge both empirically and theoretically. As far as empirical studies are concerned, historian Philippa Levine, in a seminal piece on prostitution, crime, and empire, remarked that prostitution, erroneously conceived as a quintessentially female crime, constituted an important exception to the unquestioned association of crime and masculinity, resulting in the neglect of serious gendered analysis of crime. Here the criminalization of commercial sex can be explained by the fact that prostitution is considered to defy the very norm at the core of the power gender system, that female sexuality has to be kept monogamous, reproductive, and conjugal to service the patriarchal social order. As Levine argues, prostitution “offers the prospect not only of women defined by their sexual nature but also of a more threatening vision of women actively putting that sexuality to work for their own benefit.” As a consequence, the agency of women exchanging sex for money promiscuously outside of wedlock has been conceptualized in two different apparently paradoxical ways: women prostitute themselves either because they are abnormal, so they act out of their deviancy, or because they are forced to do so, so they act under coercion. Completely lost to these split understandings, juxtaposing blame and compassion, was obviously the meaning of women's agency and rationality, especially when these were inscribed within a logic of survival and subsistence.
Women and Crime: The Egyptian Women's Prison in Drama
Authors: Mostafa Dalia Said
Published: March 2022

When the television drama series The Women's Prison (Sijin al-Nisā’) was aired in Egypt during the Muslim fasting month of Ramadan in 2014 (covering thirty episodes, each around 30 to 40 minutes), it became a hit and attracted a huge audience (Fig. 1). This was partly due to the popularity of its major theme, which focused on women and crime through characters inhabiting the famous al-Qanatir al-Khayriyya women's prison, located on the outskirts of Cairo. Another reason for its success was the group of creative women who produced it: director Kamla Abu-Zikri, scriptwriter Maryam Naʿum, art director Shirin Farghal, costume designer Rim al-ʿAdil, and director of photography Nancy ʿAbd al-Fattah. Abu-Zikri and Naʿum had collaborated on earlier works, most notably for their 2009 acclaimed film One-Zero (Wahid-Sifr) and the drama series Zaat, adapted from a famous novel of the same name by the veteran Egyptian writer Sonallah Ibrahim, which aired during Ramadan in 2013. Moreover, the key female role in both Zaat and The Women's Prison was played by the popular star actress Nelly Karim, guaranteeing high viewing rates.
Quality of haylage ofBrachiaria brizanthawith different contents of dry matter in the storage
Authors: dos S. Ezequiel F. L. , Edvan R. L. , de Azevedo F. L. , de Farias P. C. B. , do Nascimento R. R. , Barros D. M. A. , de Araújo M. J. , Miranda R. de S. , Bezerra L. R. , Santos E. M.
Published: March 2022

The purpose of this study was to evaluate the quality of Marandu grass (Brachiaria brizantha) haylage according to different dry matter (DM) contents in storage. The design adopted was completely randomized with four treatments and five replications. The treatments were DM contents of the plant at the moment of storage (in natura, 30–40, 40–50 and 50–60% DM). The analyses to assess the quality of the haylage were performed after 90 days of storage. The chemical composition, microbiological population, gas quantification, pH, N-NH3, volatile fatty acids, soluble carbohydrates (CHO) and the aerobic stability were evaluated. The means were compared through the Tukey's test and linear regression. The treatment with 50–60% DM presented the highest DM and CHO contents which were 563.8 and 42.0 g/kg, respectively. There was a higher presence of oxygen in the haylage ofin naturamaterial, which was 4.8%. There was no difference between treatments for the population of lactic acid bacteria; however, the treatment with 50–60% DM had the highest concentration of enterobacteria. The haylage with 30–40% DM and 50–60% DM presented high concentrations of acetic acid. There was no break in aerobic stability for any treatment within 120 h after opening the bales. There was a smaller amount of N-NH3in treatments with 40–50% DM and 50–60% DM. The Marandu grass with a DM content of 50–60% for haylage making demonstrated better quality characterization of conserved forage.
Medical management of severe obstructive sleep apnoea in two cases during the coronavirus disease 2019 pandemic
Authors: Gajaweera H S , Griffiths C , Everitt L H , Evans H J
Published: March 2022

Objective

Severe paediatric obstructive sleep apnoea in typically developing children with adenotonsillar hypertrophy is primarily managed surgically. Non-emergency ENT surgery was paused early in the coronavirus disease 2019 pandemic and children were offered medical management for obstructive sleep apnoea.

Methods

A service evaluation was performed to assess the impact of continuous positive airway pressure alongside medical management for severe obstructive sleep apnoea.

Results

Over 5 months during 2020, in a tertiary care setting, two children (one boy and one girl), aged 2.7 years and 4.1 years, were offered continuous positive airway pressure and medical treatments for severe obstructive sleep apnoea whilst surgery was paused during the coronavirus disease 2019 pandemic. Both children failed to establish continuous positive airway pressure therapy because of ongoing disturbed sleep on ventilation, and they proceeded to adenotonsillectomy. Sleep-Related Breathing Disorder scale scores improved following surgical intervention.

Conclusion

Continuous positive airway pressure therapy is poorly tolerated in children with severe obstructive sleep apnoea secondary to adenotonsillar hypertrophy. Surgery remains the most appropriate treatment.
Current variations and practice patterns in tympanic membrane perforation repair
Authors: Benyo S , Saadi R A , Sacks C D , Patel V , King T S , Isildak H
Published: March 2022

Objective

Management of tympanic membrane perforations is varied. This study aimed to better understand current practice patterns in myringoplasty and type 1 tympanoplasty.

Methods

An electronic questionnaire was distributed to American Academy of Otolaryngology – Head and Neck Surgery members. Practice patterns were compared in terms of fellowship training, practice length, practice setting, paediatric case frequency and total cases per year.

Results

Of the 321 respondents, most were comprehensive otolaryngologists (60.4 per cent), in private practice (60.8 per cent), with a primarily adult practice (59.8 per cent). Fellowship training was the factor most associated with significant variations in management, including pre-operative antibiotic usage (p = 0.019), contraindications (p < 0.001), approach to traumatic perforations (p < 0.001), use of local anaesthesia (p < 0.001), graft material (p < 0.001), tympanoplasty technique (p = 0.003), endoscopic assistance (p < 0.001) and timing of post-operative audiology evaluation (p = 0.003).

Conclusion

Subspecialty training appears to be the main variable associated with significant differences in peri-operative decision-making for surgical repair of tympanic membrane perforations.
Structures of synthetic helical filaments and tubes based on peptide and peptido-mimetic polymers
Authors: Miller Jessalyn G. , Hughes Spencer A. , Modlin Charles , Conticello Vincent P.
Published: March 2022

Synthetic peptide and peptido-mimetic filaments and tubes represent a diverse class of nanomaterials with a broad range of potential applications, such as drug delivery, vaccine development, synthetic catalyst design, encapsulation, and energy transduction. The structures of these filaments comprise supramolecular polymers based on helical arrangements of subunits that can be derived from self-assembly of monomers based on diverse structural motifs. In recent years, structural analyses of these materials at near-atomic resolution (NAR) have yielded critical insights into the relationship between sequence, local conformation, and higher-order structure and morphology. This structural information offers the opportunity for development of new tools to facilitate the predictable and reproduciblede novodesign of synthetic helical filaments. However, these studies have also revealed several significant impediments to the latter process – most notably, the common occurrence of structural polymorphism due to the lability of helical symmetry in structural space. This article summarizes the current state of knowledge on the structures of designed peptide and peptido-mimetic filamentous assemblies, with a focus on structures that have been solved to NAR for which reliable atomic models are available.
Deserving Hukou: An Exploration of How Chinese People Evaluate Migrants’ Welfare Deservingness
Authors: ØSTERBY-JØRGENSEN ANDREAS MICHAEL
Published: March 2022

Within the welfare deservingness literature, the question of how people conceive of deservingness criteria is still underexplored. Theoretical insights indicate that identity and reciprocity criteria are more fluidly conceived by people than much deservingness literature describes. Through a qualitative analysis, I explore how Chinese people evaluate the deservingness of a group of Chinese nationals (identity) who contribute (reciprocity) but are excluded from welfare: intranational Chinese migrants. I find that Chinese people have multiple conceptions of identity and reciprocity criteria. Some conceive of identity through larger communities, such as the nation, while others conceive of it through local communities, such as the family. Reciprocity can be conceived of in a less conditional way, which means that contributions generally make one deserving, and in a more conditional way, where one’s deservingness depends on one’s ability to make more specific kinds of contributions. Welfare recipients’ deservingness becomes very dependent on respondents’ conceptions of these deservingness criteria.
Locating liveness in holographic performances: technological anxiety and participatory fandom at Vocaloid concerts
Authors: Michaud Alyssa
Published: March 2022

This article addresses the growing global phenomenon of automated holographic concerts given by virtual pop stars called ‘Vocaloids’. Alternately acclaimed by music journalists as ‘the future of music’ and derided as ‘a robo-show, a concert simulacrum’, Vocaloid concerts across the past 10 years have sparked feelings of anxiety and prompted debate about the loss of human interaction at pre-programmed concerts. In this article, I extend Vocaloid research from recent work that addresses Vocaloid's creative online community into the middle of arenas of screaming fans, drawing on participant observation, reception history and live performance analysis in order to demonstrate the importance of participatory fandom in Vocaloid culture and its implications for 21st-century concepts of liveness. I argue that the creation of cultural meaning and the most significant interactions occur within the audience itself, when online amateur music-making communities intersect with participatory fandom at live concert events.
Task difficulty and private speech in typically developing and at-risk preschool children
Authors: MULVIHILL Aisling , MATTHEWS Natasha , DUX Paul E. , CARROLL Annemaree
Published: March 2022

Private speech is a cognitive tool to guide thinking and behavior, yet its regulatory use in atypical development remains equivocal. This study investigated the influence of task difficulty on private speech in preschool children with attention or language difficulties. Measures of private speech use, form and content were obtained while 52 typically developing and 25 developmentally at-risk three- to four-year-old children completed Duplo construction and card sort tasks, each comprising two levels of challenge. In line with previous research, developmentally at-risk children used less internalized private speech than typically developing peers. However, both typically developing and at-risk children demonstrated a similar regulatory private speech response to difficulty with no systematic evidence of group difference. This was captured by an increase in all utterances, reduced private speech internalization, and more frequent forethought and self-reflective content. Results support the hypothesis of delayed private speech internalization but not regulatory deviance in atypical development.
Changes in progress in late Northumbrian: the extension of -s as genitive and plural marker
Authors: RODRÍGUEZ LEDESMA NIEVES
Published: March 2022

Some of the linguistic changes which are crucial in the history of English and have traditionally been ascribed to Middle English can already be observed in late Northumbrian. One of these changes is the extension of genitive singular -es from the a-stems to other noun classes. Another is the spread of nominative/accusative plural -as from the masculine a-stems to the neuters and to other declensions. The aim of this article is to establish the actual scale on which these two interparadigmatic analogical changes are found in the glosses to the Lindisfarne Gospels and to the Durham Collectar, both dating from the tenth century.

The present study intends to shed more light on the process of morphological restructuring affecting the declensional system of late Northumbrian, and has three main aims: (a) to determine the pattern of dissemination of the innovative inflectional endings; (b) to establish which variables are significant in these analogical processes: declension, type and token frequency, grammatical context, Latin lemma, demarcation; and (c) to account for the different developmental tendencies of these two linguistic changes.
On the Configuration of More and Less Expressive Logic Programs
Authors: DODARO CARMINE , MARATEA MARCO , VALLATI MAURO
Published: March 2022

The decoupling between the representation of a certain problem, that is, its knowledge model, and the reasoning side is one of main strong points of model-based artificial intelligence (AI). This allows, for example, to focus on improving the reasoning side by having advantages on the whole solving process. Further, it is also well known that many solvers are very sensitive to even syntactic changes in the input. In this paper, we focus on improving the reasoning side by taking advantages of such sensitivity. We consider two well-known model-based AI methodologies, SAT and ASP, define a number of syntactic features that may characterise their inputs, and use automated configuration tools to reformulate the input formula or program. Results of a wide experimental analysis involving SAT and ASP domains, taken from respective competitions, show the different advantages that can be obtained by using input reformulation and configuration.
Living in the Shadows: Rohingya Refugees in Malaysia
Authors: MAHASETH Harsh , BANUSEKAR Samyuktha
Published: March 2022

Denied citizenship and persecuted in Myanmar, the Rohingya have fled to various countries, including Malaysia. However, Malaysia is not a signatory to the 1951 Convention Relating to the Status of Refugees and its 1967 Protocol. It also has weak domestic legal and regulatory mechanisms to protect refugees and asylum-seekers. In this paper, the authors study the treatment of Rohingya refugees in Malaysia and suggest how the Malaysian legal system can better protect them by adapting international legal practices.
Association between carotid revascularization for asymptomatic	stenosis and cognitive functions
Authors: Foret Thomas , Guillaumin Michel , Desmarets Maxime , Costa Patricia , Rinckenbach Simon , du Mont Lucie Salomon
Published: March 2022

Summary: Asymptomatic carotid stenosis (ACS) can cause cognitive dysfunction, related to cerebral hypoperfusion and microemboli. These mechanisms could be treated by carotid revascularization, but the impact of carotid angioplasty stenting (CAS) or carotid endarterectomy (CEA) on cognitive functions remains unclear. The aim of this systematic review was to realize a report on the actual state of results about asymptomatic carotid stenosis revascularization and cognitive function. We performed a systematic literature review to analyze all studies assessing the impact of asymptomatic carotid stenosis revascularizations on cognitive functions. We reviewed all publications published in Medline database and Cochrane between January 2010 and January 2020 including subjects with a cognitive evaluation and receiving carotid revascularization for asymptomatic stenosis. We identified 567 records for review, and finally we included in the systematic review 20 studies about ACS revascularization and cognitive functions. Only observational studies analyzed the impact of CEA and CAS on cognitive functions. Thus, too heterogeneous data associated to the lack of randomized controlled trials with an evaluation of optimal medical treatment did not enable to affirm the interest of the revascularization management of ACS in cognitive domain. There was a lack of standardization and finally studies were too heterogeneous to conclude on the impact of carotid revascularization on cognitive functions. There is an urgent need to harmonize research in this domain in order to prevent and treat cognitive dysfunction related to ACS, especially in our society with an aging population.
Review of Geochronologic and Geochemical Data of the Greater Antilles Volcanic Arc and Implications for the Evolution of Oceanic Arcs
Authors: Hu H. Y. , Stern R. J. , Rojas‐Agramonte Y. , Garcia‐Casco A.
Published: March 2022

The Greater Antilles islands of Cuba, Hispaniola, Puerto Rico and Jamaica plus the Virgin Islands host fragments of the fossil convergent margin that records Cretaceous subduction (operated for about 90 m.y.) of the American plates beneath the Caribbean plate and ensuing arc‐continent collision in Late Cretaceous‐Eocene time. The “soft” collision between the Greater Antilles Arc (GAA) and the Bahamas platform (and the margin of the Maya Block in western Cuba) preserved much of the convergent margin. This fossil geosystem represents an excellent natural laboratory for studying the formation and evolution of an intra‐oceanic convergent margin. We compiled geochronologic (664 ages) and geochemical data (more than 1,500 analyses) for GAA igneous and metamorphic rocks. The data was classified with a simple fourfold subdivision: fore‐arc mélange, fore‐arc ophiolite, magmatic arc, and retro‐arc to inspect the evolution of GAA through its entire lifespan. The onset of subduction recorded by fore‐arc units, together with the oldest magmatic arc sequence shows that the GAA started in Early Cretaceous time and ceased in Paleogene time. The arc was locally affected (retro‐arc region in Hispaniola) by the Caribbean Large Igneous Province (CLIP) in Early Cretaceous and strongly in Late Cretaceous time. Despite multiple biases in the database presented here, this work is intended to help overcome some of the obstacles and motivate systematic study of the GAA. Our results encourage exploration of offshore regions, especially in the east where the forearc is submerged. Offshore explorations are also encouraged in the south, to investigate relations with the CLIP.
Can Surface Soil Moisture Information Identify Evapotranspiration Regime Transitions?
Authors: Dong Jianzhi , Akbar Ruzbeh , Short Gianotti Daniel J. , Feldman Andrew F. , Crow Wade T. , Entekhabi Dara
Published: March 2022

The transition of evapotranspiration between energy‐ and water‐limitation regimes also denotes a nonlinear change in surface water and energy coupling strength. The regime transitions are primarily dominated by available moisture in the soil, although other micro‐meteorological factors also play a role. Remotely sensed soil moisture is frequently used for detecting evapotranspiration regime transitions during inter storm dry downs. However, its sampling depth does not include the entire soil profile, over which water uptake is dominated by plant root distribution. We use flux tower, surface (θs; observations at 5 cm), and vertically integrated in situ soil moisture (; 0–50 cm) observations to address the question: Can surface soil moisture robustly identify evapotranspiration regime transitions? Results demonstrate that θs and θv are hydraulically linked and have synchronized evapotranspiration regime transitions. As such, θs and θv capture comparable statistics of evapotranspiration regime prevalence, which supports the utility of remote‐sensing θs for large‐scale land‐atmosphere exchange analysis.
Extramedullary disease in multiple myeloma: a systematic literature review
Authors: Bladé Joan , Beksac Meral , Caers Jo , Jurczyszyn Artur , von Lilienfeld-Toal Marie , Moreau Philippe , Rasche Leo , Rosiñol Laura , Usmani Saad Z. , Zamagni Elena , Richardson Paul
Published: March 2022

Extramedullary involvement (or extramedullary disease, EMD) represents an aggressive form of multiple myeloma (MM), characterized by the ability of a clone and/or subclone to thrive and grow independent of the bone marrow microenvironment. Several different definitions of EMD have been used in the published literature. We advocate that true EMD is restricted to soft-tissue plasmacytomas that arise due to hematogenous spread and have no contact with bony structures. Typical sites of EMD vary according to the phase of MM. At diagnosis, EMD is typically found in skin and soft tissues; at relapse, typical sites involved include liver, kidneys, lymph nodes, central nervous system (CNS), breast, pleura, and pericardium. The reported incidence of EMD varies considerably, and differences in diagnostic approach between studies are likely to contribute to this variability. In patients with newly diagnosed MM, the reported incidence ranges from 0.5% to 4.8%, while in relapsed/refractory MM the reported incidence is 3.4 to 14%. Available data demonstrate that the prognosis is poor, and considerably worse than for MM without soft-tissue plasmacytomas. Among patients with plasmacytomas, those with EMD have poorer outcomes than those with paraskeletal involvement. CNS involvement is rare, but prognosis is even more dismal than for EMD in other locations, particularly if there is leptomeningeal involvement. Available data on treatment outcomes for EMD are derived almost entirely from retrospective studies. Some agents and combinations have shown a degree of efficacy but, as would be expected, this is less than in MM patients with no extramedullary involvement. The paucity of prospective studies makes it difficult to justify strong recommendations for any treatment approach. Prospective data from patients with clearly defined EMD are important for the optimal evaluation of treatment outcomes.
RUFY3 and RUFY4 are ARL8 effectors that promote coupling of endolysosomes to dynein-dynactin
Authors: Keren-Kaplan Tal , Sarić Amra , Ghosh Saikat , Williamson Chad D. , Jia Rui , Li Yan , Bonifacino Juan S.
Published: March 2022

The small GTPase ARL8 associates with endolysosomes, leading to the recruitment of several effectors that couple endolysosomes to kinesins for anterograde transport along microtubules, and to tethering factors for eventual fusion with other organelles. Herein we report the identification of theRUN- andFYVE-domain-containing proteins RUFY3 and RUFY4 as ARL8 effectors that promote coupling of endolysosomes to dynein-dynactin for retrograde transport along microtubules. Using various methodologies, we find that RUFY3 and RUFY4 interact with both GTP-bound ARL8 and dynein-dynactin. In addition, we show that RUFY3 and RUFY4 promote concentration of endolysosomes in the juxtanuclear area of non-neuronal cells, and drive redistribution of endolysosomes from the axon to the soma in hippocampal neurons. The function of RUFY3 in retrograde transport contributes to the juxtanuclear redistribution of endolysosomes upon cytosol alkalinization. These studies thus identify RUFY3 and RUFY4 as ARL8-dependent, dynein-dynactin adaptors or regulators, and highlight the role of ARL8 in the control of both anterograde and retrograde endolysosome transport.
A non-dividing cell population with high pyruvate dehydrogenase kinase activity regulates metabolic heterogeneity and tumorigenesis in the intestine
Authors: Sebastian Carlos , Ferrer Christina , Serra Maria , Choi Jee-Eun , Ducano Nadia , Mira Alessia , Shah Manasvi S. , Stopka Sylwia A. , Perciaccante Andrew J. , Isella Claudio , Moya-Rull Daniel , Vara-Messler Marianela , Giordano Silvia , Maldi Elena , Desai Niyati , Capen Diane E. , Medico Enzo , Cetinbas Murat , Sadreyev Ruslan I. , Brown Dennis , Rivera Miguel N. , Sapino Anna , Breault David T. , Agar Nathalie Y. R. , Mostoslavsky Raul
Published: March 2022

Although reprogramming of cellular metabolism is a hallmark of cancer, little is known about how metabolic reprogramming contributes to early stages of transformation. Here, we show that the histone deacetylase SIRT6 regulates tumor initiation during intestinal cancer by controlling glucose metabolism. Loss of SIRT6 results in an increase in the number of intestinal stem cells (ISCs), which translates into enhanced tumor initiating potential in APCmin mice. By tracking down the connection between glucose metabolism and tumor initiation, we find a metabolic compartmentalization within the intestinal epithelium and adenomas, where a rare population of cells exhibit features of Warburg-like metabolism characterized by high pyruvate dehydrogenase kinase (PDK) activity. Our results show that these cells are quiescent cells expressing +4 ISCs and enteroendocrine markers. Active glycolysis in these cells suppresses ROS accumulation and enhances their stem cell and tumorigenic potential. Our studies reveal that aerobic glycolysis represents a heterogeneous feature of cancer, and indicate that this metabolic adaptation can occur in non-dividing cells, suggesting a role for the Warburg effect beyond biomass production in tumors.
Fully conjugated azacorannulene dimer as large diaza[80]fullerene fragment
Authors: Wang Weifan , Hanindita Fiona , Hamamoto Yosuke , Li Yongxin , Ito Shingo
Published: March 2022

A fully conjugated azacorannulene dimer with a large π-surface (76π system) was successfully synthesized from a fully conjugated bifunctional polycyclic aromatic azomethine ylide. This molecule represents an example of diaza[80]fullerene (C78N2) fragment molecule bearing two internal nitrogen atoms. X-ray crystallography analysis shows its boat-shaped structure with two terminal azacorannulenes bent in the same direction. The molecular shape leads to unique selective association with a dumbbell-shaped C60 dimer (C120) over C60 through shape recognition. Owing to its large π-surface and a narrow HOMO–LUMO gap, the azacorannulene dimer exhibits red fluorescence with a quantum yield of up to 31%. The utilization of the fully conjugated bifunctional azomethine ylide is a powerful method for the bottom-up synthesis of large multiazafullerene fragments, providing a step towards the selective total synthesis of multiazafullerenes.
Ground state cooling of an ultracoherent electromechanical system
Authors: Seis Yannick , Capelle Thibault , Langman Eric , Saarinen Sampo , Planz Eric , Schliesser Albert
Published: March 2022

Cavity electromechanics relies on parametric coupling between microwave and mechanical modes to manipulate the mechanical quantum state, and provide a coherent interface between different parts of hybrid quantum systems. High coherence of the mechanical mode is of key importance in such applications, in order to protect the quantum states it hosts from thermal decoherence. Here, we introduce an electromechanical system based around a soft-clamped mechanical resonator with an extremely high Q-factor (>109) held at very low (30 mK) temperatures. This ultracoherent mechanical resonator is capacitively coupled to a microwave mode, strong enough to enable ground-state-cooling of the mechanics ($${\bar{n}}_{\min }=0.76\pm 0.16$$n¯min=0.76±0.16). This paves the way towards exploiting the extremely long coherence times (tcoh > 100 ms) offered by such systems for quantum information processing and state conversion.
A stable quasi-solid electrolyte improves the safe operation of highly efficient lithium-metal pouch cells in harsh environments
Authors: Chang Zhi , Yang Huijun , Zhu Xingyu , He Ping , Zhou Haoshen
Published: March 2022

Nanoconfined/sub-nanoconfined solvent molecules tend to undergo dramatic changes in their properties and behaviours. In this work, we find that unlike typical bulk liquid electrolytes, electrolytes confined in a sub-nanoscale environment (inside channels of a 6.5 Å metal-organic framework, defined as a quasi-solid electrolyte) exhibits unusual properties and behaviours: higher boiling points, highly aggregated configurations, decent lithium-ion conductivities, extended electrochemical voltage windows (approximately 5.4 volts versus Li/Li+) and nonflammability at high temperatures. We incorporate this interesting electrolyte into lithium-metal batteries (LMBs) and find that LMBs cycled in the quasi-solid electrolyte demonstrate an electrolyte interphase-free (CEI-free) cathode and dendrite-free Li-metal surface. Moreover, high-voltage LiNi0.8Co0.1Mn0.1O2//Li (NCM-811//Li with a high NCM-811 mass loading of 20 mg cm−2) pouch cells assemble with the quasi-solid electrolyte deliver highly stable electrochemical performances even at a high working temperature of 90 °C (171 mAh g−1 after 300 cycles, 89% capacity retention; 164 mAh g−1 after 100 cycles even after being damaged). This strategy for fabricating nonflammable and ultrastable quasi-solid electrolytes is promising for the development of safe and high-energy-density LIBs/LMBs for powering electronic devices under various practical working conditions.
Using CRISPR-Kill for organ specific cell elimination by cleavage of tandem repeats
Authors: Schindele Angelina , Gehrke Fabienne , Schmidt Carla , Röhrig Sarah , Dorn Annika , Puchta Holger
Published: March 2022

CRISPR/Cas has been mainly used for mutagenesis through the induction of double strand breaks (DSBs) within unique protein-coding genes. Using the SaCas9 nuclease to induce multiple DSBs in functional repetitive DNA of Arabidopsis thaliana, we can now show that cell death can be induced in a controlled way. This approach, named CRISPR-Kill, can be used as tool for tissue engineering. By simply exchanging the constitutive promoter of SaCas9 with cell type-specific promoters, it is possible to block organogenesis in Arabidopsis. By AP1-specific expression of CRISPR-Kill, we are able to restore the apetala1 phenotype and to specifically eliminate petals. In addition, by expressing CRISPR-Kill in root-specific pericycle cells, we are able to dramatically reduce the number and the length of lateral roots. In the future, the application of CRISPR-Kill may not only help to control development but could also be used to change the biochemical properties of plants.
Fatty acid oxidation fuels glioblastoma radioresistance with CD47-mediated immune evasion
Authors: Jiang Nian , Xie Bowen , Xiao Wenwu , Fan Ming , Xu Shanxiu , Duan Yixin , Hamsafar Yamah , Evans Angela C. , Huang Jie , Zhou Weibing , Lin Xuelei , Ye Ningrong , Wanggou Siyi , Chen Wen , Jing Di , Fragoso Ruben C. , Dugger Brittany N. , Wilson Paul F. , Coleman Matthew A. , Xia Shuli , Li Xuejun , Sun Lun-Quan , Monjazeb Arta M. , Wang Aijun , Murphy William J. , Kung Hsing-Jien , Lam Kit S. , Chen Hong-Wu , Li Jian Jian
Published: March 2022

Glioblastoma multiforme (GBM) remains the top challenge to radiotherapy with only 25% one-year survival after diagnosis. Here, we reveal that co-enhancement of mitochondrial fatty acid oxidation (FAO) enzymes (CPT1A, CPT2 and ACAD9) and immune checkpoint CD47 is dominant in recurrent GBM patients with poor prognosis. A glycolysis-to-FAO metabolic rewiring is associated with CD47 anti-phagocytosis in radioresistant GBM cells and regrown GBM after radiation in syngeneic mice. Inhibition of FAO by CPT1 inhibitor etomoxir or CRISPR-generated CPT1A−/−, CPT2−/−, ACAD9−/− cells demonstrate that FAO-derived acetyl-CoA upregulates CD47 transcription via NF-κB/RelA acetylation. Blocking FAO impairs tumor growth and reduces CD47 anti-phagocytosis. Etomoxir combined with anti-CD47 antibody synergizes radiation control of regrown tumors with boosted macrophage phagocytosis. These results demonstrate that enhanced fat acid metabolism promotes aggressive growth of GBM with CD47-mediated immune evasion. The FAO-CD47 axis may be targeted to improve GBM control by eliminating the radioresistant phagocytosis-proofing tumor cells in GBM radioimmunotherapy.
Spatiotemporal reprogramming of differentiated cells underlies regeneration and neoplasia in the intestinal epithelium
Authors: Higa Tsunaki , Okita Yasutaka , Matsumoto Akinobu , Nakayama Shogo , Oka Takeru , Sugahara Osamu , Koga Daisuke , Takeishi Shoichiro , Nakatsumi Hirokazu , Hosen Naoki , Robine Sylvie , Taketo Makoto M. , Sato Toshiro , Nakayama Keiichi I.
Published: March 2022

Although the mammalian intestinal epithelium manifests robust regenerative capacity after various cytotoxic injuries, the underlying mechanism has remained unclear. Here we identify the cyclin-dependent kinase inhibitor p57 as a specific marker for a quiescent cell population located around the +4 position of intestinal crypts. Lineage tracing reveals that the p57+ cells serve as enteroendocrine/tuft cell precursors under normal conditions but dedifferentiate and act as facultative stem cells to support regeneration after injury. Single-cell transcriptomics analysis shows that the p57+ cells undergo a dynamic reprogramming process after injury that is characterized by fetal-like conversion and metaplasia-like transformation. Population-level analysis also detects such spatiotemporal reprogramming widely in other differentiated cell types. In intestinal adenoma, p57+ cells manifest homeostatic stem cell activity, in the context of constitutively activated spatiotemporal reprogramming. Our results highlight a pronounced plasticity of the intestinal epithelium that supports maintenance of tissue integrity in normal and neoplastic contexts.
Fibroblast activation protein activated antifibrotic peptide delivery attenuates fibrosis in mouse models of liver fibrosis
Authors: Lee Jaiwoo , Byun Junho , Shim Gayong , Oh Yu-Kyoung
Published: March 2022

In liver fibrosis, activated hepatic stellate cells are known to overexpress fibroblast activation protein. Here we report a targeted antifibrotic peptide-delivery system in which fibroblast activation protein, which is overexpressed in fibrotic regions of the liver, liberates the antifibrotic peptide melittin by cleaving a fibroblast activation protein-specific site in the peptide. The promelittin peptide is linked to pegylated and maleimide-functionalized liposomes, resulting in promelittin-modified liposomes. The promelittin-modified liposomes were effective in reducing the viability of activated hepatic stellate cells but not that of control cells. In three types of liver fibrosis mouse models, intravenously administered promelittin-modified liposomes significantly reduces fibrotic regions. In addition, in the bile duct ligation mouse model promelittin-modified liposome-treatment increases overall survival. Although this peptide-delivery concept was tested for liver fibrosis, it can potentially be adapted to other fibrotic diseases.
Dynamic-quenching of a single-photon avalanche photodetector using an adaptive resistive switch
Authors: Zheng Jiyuan , Xue Xingjun , Ji Cheng , Yuan Yuan , Sun Keye , Rosenmann Daniel , Wang Lai , Wu Jiamin , Campbell Joe C. , Guha Supratik
Published: March 2022

One of the most common approaches for quenching single-photon avalanche diodes is to use a passive resistor in series with it. A drawback of this approach has been the limited recovery speed of the single-photon avalanche diodes. High resistance is needed to quench the avalanche, leading to slower recharging of the single-photon avalanche diodes depletion capacitor. We address this issue by replacing a fixed quenching resistor with a bias-dependent adaptive resistive switch. Reversible generation of metallic conduction enables switching between low and high resistance states under unipolar bias. As an example, using a Pt/Al2O3/Ag resistor with a commercial silicon single-photon avalanche diodes, we demonstrate avalanche pulse widths as small as ~30 ns, 10× smaller than a passively quenched approach, thus significantly improving the single-photon avalanche diodes frequency response. The experimental results are consistent with a model where the adaptive resistor dynamically changes its resistance during discharging and recharging the single-photon avalanche diodes.
The induction of natural competence adapts staphylococcal metabolism to infection
Authors: Cordero Mar , García-Fernández Julia , Acosta Ivan C. , Yepes Ana , Avendano-Ortiz Jose , Lisowski Clivia , Oesterreicht Babett , Ohlsen Knut , Lopez-Collazo Eduardo , Förstner Konrad U. , Eulalio Ana , Lopez Daniel
Published: March 2022

A central question concerning natural competence is why orthologs of competence genes are conserved in non-competent bacterial species, suggesting they have a role other than in transformation. Here we show that competence induction in the human pathogen Staphylococcus aureus occurs in response to ROS and host defenses that compromise bacterial respiration during infection. Bacteria cope with reduced respiration by obtaining energy through fermentation instead. Since fermentation is energetically less efficient than respiration, the energy supply must be assured by increasing the glycolytic flux. The induction of natural competence increases the rate of glycolysis in bacteria that are unable to respire via upregulation of DNA- and glucose-uptake systems. A competent-defective mutant showed no such increase in glycolysis, which negatively affects its survival in both mouse and Galleria infection models. Natural competence foster genetic variability and provides S. aureus with additional nutritional and metabolic possibilities, allowing it to proliferate during infection.
An RNA-binding protein acts as a major post-transcriptional modulator in Bacillus anthracis
Authors: Pi Hualiang , Weiss Andy , Laut Clare L. , Grunenwald Caroline M. , Lin Hannah K. , Yi Xinjie I. , Stauff Devin L. , Skaar Eric P.
Published: March 2022

HitRS is a two-component system that responds to cell envelope damage in the human pathogen Bacillus anthracis. Here we identify an RNA-binding protein, KrrA, that regulates HitRS function by modulating the stability of the hitRS mRNA. In addition to hitRS, KrrA binds to over 70 RNAs and, directly or indirectly, affects the expression of over 150 genes involved in multiple processes, including genetic competence, sporulation, RNA turnover, DNA repair, transport, and cellular metabolism. KrrA does not exhibit detectable nuclease activity in vitro, and thus the mechanism by which it modulates mRNA stability remains unclear.
New black indium oxide—tandem photothermal CO2-H2 methanol selective catalyst
Authors: Zhang Zeshu , Mao Chengliang , Meira Débora Motta , Duchesne Paul N. , Tountas Athanasios A. , Li Zhao , Qiu Chenyue , Tang Sanli , Song Rui , Ding Xue , Sun Junchuan , Yu Jiangfan , Howe Jane Y. , Tu Wenguang , Wang Lu , Ozin Geoffrey A.
Published: March 2022

It has long been known that the thermal catalyst Cu/ZnO/Al2O3(CZA) can enable remarkable catalytic performance towards CO2 hydrogenation for the reverse water-gas shift (RWGS) and methanol synthesis reactions. However, owing to the direct competition between these reactions, high pressure and high hydrogen concentration (≥75%) are required to shift the thermodynamic equilibrium towards methanol synthesis. Herein, a new black indium oxide with photothermal catalytic activity is successfully prepared, and it facilitates a tandem synthesis of methanol at a low hydrogen concentration (50%) and ambient pressure by directly using by-product CO as feedstock. The methanol selectivities achieve 33.24% and 49.23% at low and high hydrogen concentrations, respectively.
Qualitative study on perceptions of use of Fractional Exhaled Nitric Oxide (FeNO) in asthma reviews
Authors: Santillo Marta , Ainsworth Ben , Van Velthoven Michelle Helena , Yardley Lucy , Thomas Mike , Wang Kay , Tonkin-Crine Sarah
Published: March 2022

Current methods to assess asthma and guide inhaled corticosteroid (ICS) dose titration mainly centre on patient-reported symptoms and lung function assessments. However, these methods correlate only weakly with airway inflammation making them unreliable predictors of future exacerbations and ICS requirement. Fractional Exhaled Nitric Oxide (FeNO) is a simple non-invasive objective measure of airways inflammation used predominantly in specialist clinics. Previous qualitative studies have mainly focused on the acceptability of FeNO in secondary care and there is limited insight to support clinicians and patients using FeNO in primary care asthma reviews. This study aimed to explore adult patient with asthma and primary care health care professional (HCP) views on introducing FeNO as part of routine asthma reviews. Twenty-three health care professionals and 22 patients were interviewed over the phone or online. Both groups reported that current asthma reviews are often seen as tick-box exercises and that introducing the FeNO test would make reviews more tailored to the individual patient, rather than relying on subjective patient reports of asthma control. Adults with asthma also highlighted support more open communication and their understanding of asthma, as they desired to feel more engaged in decisions and conversations about their asthma. HCPs reported valuing patient education and empowerment over a paternalistic approach, when time and resources allow. They also recognised FeNO to provide an objective measure of inflammation that could support them in the education and empowerment of patients. FeNO was seen by both groups as a potentially valuable addition to current asthma reviews mainly led by nurses, both for increasing their understanding of current risk of exacerbation and also to provide more tailored and personalised asthma management to patients. Our findings highlighted the need for open and clear communication about how to interpret FeNO results.