bluuebunny/crossref_metadata_2025 huggingface dataset:
Engineering pH‐Sensitive Stable Nanovesicles for Delivery of MicroRNA Therapeutics
Authors: Boloix Ariadna , Feiner‐Gracia Natalia , Köber Mariana , Repetto Javier , Pascarella Rosa , Soriano Aroa , Masanas Marc , Segovia Nathaly , Vargas‐Nadal Guillem , Merlo‐Mas Josep , Danino Dganit , Abutbul‐Ionita Inbal , Foradada Laia , Roma Josep , Córdoba Alba , Sala Santi , de Toledo Josep Sánchez , Gallego Soledad , Veciana Jaume , Albertazzi Lorenzo , Segura Miguel F. , Ventosa Nora
Published: November 2021

MicroRNAs (miRNAs) are small non‐coding endogenous RNAs, which are attracting a growing interest as therapeutic molecules due to their central role in major diseases. However, the transformation of these biomolecules into drugs is limited due to their unstability in the bloodstream, caused by nucleases abundantly present in the blood, and poor capacity to enter cells. The conjugation of miRNAs to nanoparticles (NPs) could be an effective strategy for their clinical delivery. Herein, the engineering of non‐liposomal lipid nanovesicles, named quatsomes (QS), for the delivery of miRNAs and other small RNAs into the cytosol of tumor cells, triggering a tumor‐suppressive response is reported. The engineered pH‐sensitive nanovesicles have controlled structure (unilamellar), size (<150 nm) and composition. These nanovesicles are colloidal stable (>24 weeks), and are prepared by a green, GMP compliant, and scalable one‐step procedure, which are all unavoidable requirements for the arrival to the clinical practice of NP based miRNA therapeutics. Furthermore, QS protect miRNAs from RNAses and when injected intravenously, deliver them into liver, lung, and neuroblastoma xenografts tumors. These stable nanovesicles with tunable pH sensitiveness constitute an attractive platform for the efficient delivery of miRNAs and other small RNAs with therapeutic activity and their exploitation in the clinics.
Schemes of modules over gentle algebras and laminations of surfaces
Authors: Geiß Christof , Labardini-Fragoso Daniel , Schröer Jan
Published: November 2021

We study the affine schemes of modules over gentle algebras. We describe the smooth points of these schemes, and we also analyze their irreducible components in detail. Several of our results generalize formerly known results, e.g. by dropping acyclicity, and by incorporating band modules. A special class of gentle algebras are Jacobian algebras arising from triangulations of unpunctured marked surfaces. For these we obtain a bijection between the set of generically$$\tau $$τ-reduced decorated irreducible components and the set of laminations of the surface. As an application, we get that the set of bangle functions (defined by Musiker–Schiffler–Williams) in the upper cluster algebra associated with the surface coincides with the set of generic Caldero-Chapoton functions (defined by Geiß–Leclerc–Schröer).
Stability properties of a projector-splitting scheme for dynamical low rank approximation of random parabolic equations
Authors: Kazashi Yoshihito , Nobile Fabio , Vidličková Eva
Published: November 2021

We consider the Dynamical Low Rank (DLR) approximation of random parabolic equations and propose a class of fully discrete numerical schemes. Similarly to the continuous DLR approximation, our schemes are shown to satisfy a discrete variational formulation. By exploiting this property, we establish stability of our schemes: we show that our explicit and semi-implicit versions are conditionally stable under a “parabolic” type CFL condition which does not depend on the smallest singular value of the DLR solution; whereas our implicit scheme is unconditionally stable. Moreover, we show that, in certain cases, the semi-implicit scheme can be unconditionally stable if the randomness in the system is sufficiently small. Furthermore, we show that these schemes can be interpreted as projector-splitting integrators and are strongly related to the scheme proposed in [29, 30], to which our stability analysis applies as well. The analysis is supported by numerical results showing the sharpness of the obtained stability conditions.
Rehabilitation of visual functions in adult amblyopic patients with a virtual reality videogame: a case series
Authors: Jiménez-Rodríguez Carmen , Yélamos-Capel Lourdes , Salvestrini Patricia , Pérez-Fernández Cristian , Sánchez-Santed Fernando , Nieto-Escámez Francisco
Published: November 2021

Amblyopia or lazy eye is a dysfunction of the visual system that appears during childhood and traditionally has been considered untreatable in adults. Its main consequences are the loss of visual acuity and contrast sensitivity of the amblyopic eye and binocular vision impairments. During the last years videogames have been used as a therapeutic tool for amblyopia with the inconclusive results. The present work has assessed the effectiveness of a virtual reality videogame (AmbliOK®) in the neurorehabilitation of four adult clinical cases with anisometropic amblyopia. Visual acuity, contrast sensitivity, stereopsis and interocular suppression were assessed before, during, immediately after, one month and one year (in one patient) after the training. The intervention was conducted along four weeks (10 h) and yielded the variable results. In general, all patients showed an improvement in visual functions although not all ameliorated in the same way. Visual acuity measures improved in all patients, falling outside the amblyopia criterion at the end of the treatment. However, the improvement was not maintained one month later in two patients. Contrast sensitivity progressively improved for the amblyopic and the fellow eyes with all patients showing better results one month after the treatment. The patient assessed one year after still showed better results than in the baseline. Patients showing bad stereopsis in the baseline reached a performance considered normal one month and even one year after the treatment. The effectiveness of the treatment seems to be related to the characteristics of patients.
Correction to: On the Use of X-ray Computed Tomography in Assessment of 3D-Printed Components
Authors: Khosravani Mohammad Reza , Reinicke Tamara
Published: November 2021

A Correction to this paper has been published: 10.1007/s10921-020-00721-1
Sustainability assurance practices: a systematic review and future research agenda
Authors: Hazaea Saddam A. , Zhu Jinyu , Khatib Saleh F. A. , Bazhair Ayman Hassan , Elamer Ahmed A.
Published: November 2021

Although firms increasingly publish sustainability reports, assuring such reports is relatively new. This study reviews the literature of sustainability assurance to evaluate the intellectual development of the field and provide recommendations for future studies. It also demonstrates the role of assurance to enhance the credibility of sustainability reports and corporate reputation. This paper systematically reviews 94 papers obtained from the Scopus database between 1993 and August 2021. Our study shows that there is an increase in the number of studies published in recent years. We also found that some countries have received limited attention, such as the USA. The scant literature examining sustainability assurance in private institutions and non-profit organisations should be reinforced. Likewise, the sustainability research also provides limited evidence on the governance debate. The vast majority of research is not based on theoretical grounds. The need for assurance of sustainability reports not only enhances the reputation but also adds more value to the organisation’s planning, monitoring, and accountability. We highlight several new research suggestions that may enhance the understanding of sustainability assurance practices.
Application of Human Epineural Conduit Supported with Human Mesenchymal Stem Cells as a Novel Therapy for Enhancement of Nerve Gap Regeneration
Authors: Siemionow Maria , Strojny Marcin Michal , Kozlowska Katarzyna , Brodowska Sonia , Grau-Kazmierczak Wiktoria , Cwykiel Joanna
Published: November 2021

Various therapeutic methods have been suggested to enhance nerve regeneration. In this study, we propose a novel approach for enhancement of nerve gap regeneration by applying human epineural conduit (hEC) supported with human mesenchymal stem cells (hMSC), as an alternative to autograft repair. Restoration of 20 mm sciatic nerve defect with hEC created from human sciatic nerve supported with hMSC was tested in 4 experimental groups (n = 6 each) in the athymic nude rat model (Crl:NIH-Foxn1rnu): 1 - No repair control, 2 - Autograft control, 3 - Matched diameter hEC filled with 1 mL saline, 4 - Matched diameter hEC supported with 3 × 106 hMSC. Assessments included: functional tests: toe-spread and pinprick, regeneration assessment by immunofluorescence staining: HLA-1, HLA-DR, NGF, GFAP, Laminin B, S-100, VEGF, vWF and PKH26 labeling; histomorphometric analysis of myelin thickness, axonal density, fiber diameter and myelinated nerve fibers percentage; Gastrocnemius Muscle Index (GMI) and muscle fiber area ratio. Best sensory and motor function recovery, as well as GMI and muscle fiber area ratio, were observed in the autograft group, and were comparable to the hEC with hMSC group (p = 0.038). Significant improvements of myelin thickness (p = 0.003), fiber diameter (p = 0.0296), and percentage of myelinated fibers (p < 0.0001) were detected in hEC group supported with hMSC compared to hEC with saline controls. At 12-weeks after nerve gap repair, hEC combined with hMSC revealed increased expression of neurotrophic and proangiogenic factors, which corresponded with improvement of function comparable with the autograft control. Application of our novel hEC supported with hMSC provides a potential alternative to the autograft nerve repair.

Graphical Abstract
Capillary electrophoresis-UV analysis using silica-layer coated capillary for separation of seven phenolic acids and caffeine and its application to tea analysis
Authors: Hemwech Pattamaporn , Obma Apinya , Detsangiamsak Sasinun , Wirasate Supa , Chaiyen Pimchai , Wilairat Prapin , Chantiwas Rattikan
Published: November 2021

This work presents an innovative silica-layer coated capillary with comparison study of the silica-layer coated capillary and the fused-silica capillary for the separation of seven phenolic acids viz. p-hydroxyphenylacetic acid (PHPA),p-coumaric acid (PCA),p-hydroxybenzoic acid (PHBA), caffeic acid (CFA), (3,4-dihydroxyphenyl)acetic acid (DHPA), gallic acid (GLA), and 2,3,4-trihydroxybenzoic acid (THBA), together with caffeine (CF), by capillary electro-chromatography (CEC) and micellar electrokinetic chromatography (MEKC), respectively. The running buffer was 25.0 mM borate at pH 9.0, with addition of 50.0 mM sodium dodecyl sulfate for the MEKC mode. The non-coated capillary could not separate all seven phenolic acids by CEC or MEKC. This was achieved using the coated capillary for both CEC and MEKC. The innovative coated capillary with CEC had plate numberN ≥ 2.0 × 104 m−1and resolutionRs ≥ 1.6 for all adjacent pairs of peaks. The capillary was also able to separate GLA and THBA which are structural isomers. Although MEKC mode provided comparable efficiency and selectivity, the reduced EOF of the coated capillary led to longer separation time. The linear calibration range of the seven phenolic acids and caffeine were different but the coefficients of determinations (r2) were all > 0.9965. The precisions of the relative migration times and peak area ratios of analyte to internal standard were 0.1–1.8% and 1.8–6.8%, respectively. There were no statistical differences in the efficiency of separation of the phenolic acids and caffeine for three coated capillaries. It was applied to the analysis of caffeine and phenolic acids in brewed tea using tyramine as the internal standard. The tea samples were diluted prior to analysis by CEC. The separation was less than 15 min. Caffeine, gallic acid andp-coumaric acid were detected and quantified. Caffeine and gallic acid contents were 10.8–15.0 and 2.6–4.8 mg g−1dry tea leaves, respectively.p-Coumaric acid was detected in only one of the samples with a content of 0.4 mg g−1. Percent recoveries of spiked diluted samples were 90 ± 9 to 106 ± 13%, respectively.

Article highlights

Silica-layer coated capillary is first reported for simultaneous separation of seven phenolic acids by non-MEKC analysis.

Performance between coated, and non-coated capillaries with analysis by CEC and MEKC were compared.

Plate number, resolution, capillary reproducibility, and electroosmotic flow mobility are investigated.

Graphical abstract
Methods to optimize energy consumption in Conarc furnaces
Authors: Wanjari Aashay
Published: November 2021

Over the past few decades, steelmaking has reached its zenith in terms of annual productivity, and relevant processes have been developed over time to produce steel with maximum efficiency in a shorter time. One of the prominent steelmaking practices used extensively in contemporary industries is the Conarc Steelmaking Practice, which involves the use of electrical and chemical Energy to carry out melting and decarburization in respective shells. This article reviews the factors that affect the energy consumption in Conarc furnaces and provides insight into the technologies developed to alleviate energy consumption and make the steelmaking process optimal in terms of energy consumption and requirement. This article also accentuates relevant systems and melting practices for the raw materials, which can be utilized in the Conarc Steelmaking practice to make the entire process less energy-intensive. Oxygen-enhanced combustion and thermophotovoltaic systems can alleviate energy consumption substantially while maintaining steel quality at the same time, as discussed in the paper. Additionally, some mathematical models have been discussed that facilitate in formulating an energy optimal and financial steelmaking process.
Experimental study of anisotropic constitutive behavior of β-HMX crystals via nanoindentation and small-scale dynamic impact
Authors: Olokun Ayotomi , Dillard Tyler , Dhiman Abhijeet , Tomar Vikas
Published: November 2021

For energetic crystals such as HMX, the sensitivity of the material to shock, the possibility of initiation, and the subsequent reaction is known to be controlled by processes occurring at the crystal level. The anisotropic nature of β-HMX can be critical in determining the performance of HMX based polymer bonded explosives, which are widely used across multiple industries as propellant or explosives. In this work, we experimentally obtain constitutive parameters for characterizing the response of multiple crystalline planes of β-HMX crystals to external loading. Nanoindentation and small-scale dynamic impact experiments were performed on multiple planes of β-HMX crystals to comparatively measure the indentation moduli in multiple orientation directions. Anisotropic material behavior, involving constitutive elastic and non-elastic parameters, was measured and studied. Findings regarding material properties for the (100), (010), (001), {110}, and {011} planes of β-HMX are presented and compared with literature data.
Circular cities: an evidence map of research between 2010 and 2020
Authors: Vanhuyse Fedra , Haddaway Neal R. , Henrysson Maryna
Published: November 2021

Worldwide, cities are implementing circular economy (CE) strategies to reduce the resources they consume and their environmental impact. To understand the CE strategies and sectors cities have been focusing on, we have conducted an evidence map describing the literature published in the last ten years. The main outputs are a searchable database comprising 178 publications showing which cities have been discussed, what CE strategy they are focusing on, and the sectors under review. The results show that most research has focused on European countries. Those efforts mainly concentrate on waste and wastewater management, and recycling and recovery strategies are considered the “lower-level” strategies in the CE taxonomy. It highlights the potential for further research in other cities and regions, looking across sectors and analyzing strategies that tackle the “higher-level” CE strategies. Higher-level strategies include reducing, repurposing, remanufacturing and reusing opportunities to achieve the potential attributed to a CE model by governments across the world.
Documentación de culturas del acoso en la arqueología: Revisión y análisis de estudios de investigación cuantitativa y cualitativa
Authors: Voss Barbara L.
Published: November 2021

Este artículo, el primero de una serie de dos, analiza la investigación actual sobre el acoso en la arqueología que ha dado forma a la disciplina desde finales de 1800. A partir de la década de 1970, el acoso se reconoce como un factor significativo que afecta la equidad de género. Investigaciones cualitativas y cuantitativas recientes han verificado que el acoso ocurre a tasas epidémicas, en tanto les arqueólogues son acosades, principalmente por otres arqueólogues, y esto ocurre no sólo en entornos de investigación de campo, sino también en aulas, laboratorios, museos, lugares de trabajo y conferencias. Aunque las mujeres en la arqueología experimentan acoso con mayor frecuencia, las cifras de hombres como de mujeres informan de acoso en proporciones inquietantemente altas. Les arqueólogues de color, LGBTQIA+, no binarios y con discapacidades también son hostigades de manera desproporcionada. Como se refleja en las propias experiencias de la autora, el acoso crea una carga cognitiva para les sobrevivientes y reduce el acceso a oportunidades profesionales, impactando directamente en la diversidad dentro de la arqueología. Afortunadamente, existen intervenciones y políticas basadas en evidencia que pueden reducir esta práctica y apoyar a les sobrevivientes, lo que se analiza en el segundo artículo, “Contra las culturas del acoso en la arqueología: Enfoques socioambientales y basados en el trauma para la transformación disciplinaria”.
Jeffersonian Trembling: White Nationalism and the Racial Origins of National Security
Authors: CASTRONOVO RUSS
Published: November 2021

This essay examines how the project of national security was beset by the affective intensities of “Jeffersonian trembling.” While white nationalists today see themselves as threatened with dispossession and the loss of historical entitlement, mainstream supporters of the movement to colonize US blacks leveraged their fear to export insecurity and precarity onto African Americans. The claim of “white genocide” dates back to biopolitical anxieties that drove the colonization movement to control and manage the chimera of black population excess. Such efforts required the conversion of blacks into data so that they could be brought under a regime of “algorithmic governmentality.” Instead of targeting individual black bodies, white nationalism read the latest data about black people in toto as a threat. Different in scale from the surveillance techniques that overseers, patrollers, and other agents of slaveholding society employed, colonization represented a security algorithm for tackling a data problem that was the size of the African American population itself. In this history, we can detect how the logic of security is always a racialized formation that is intimately connected to feelings of insecurity.
How White Americans Became Irish: Race, Ethnicity and the Politics of Whiteness
Authors: KENNEDY LIAM
Published: November 2021

The origin stories of Irish America have been core narratives within the “making-of-America” discourse of the nation's founding and development and were especially potent in the cementing, in the mid-twentieth century, of the idea of the US as “a nation of immigrants.” It is an idea that has done significant psychological as well as cultural and political work for white ethnics in the US, glossing important elements of whiteness as a racial formation, mystifying its oppressive qualities and its particularistic claims to identity and values. It has informed the complex ways in which Irish Americans have reconciled their identities in the present with prejudice and discrimination in the past. The story of “how the Irish became white” has been popularly glossed as an ethnic achievement, periodically reclaiming otherness, while eliding the politics of racial power and privilege. Today, as ethnonationalism surges through the mainstream of American politics and culture, unsettling the hegemony of liberal whiteness, Irishness has become a floating signifier of white anger and angst. Perhaps the story we need to tell now is not how the Irish became white but how white folks in the US have become Irish.
A New Kind of Vanguard: Cuban−North Korean Discourse on Revolutionary Strategy for the Global South in the 1960s
Authors: Taylor Moe
Published: November 2021

During the 1960s, the Cuban government attempted to play a leadership role within the Latin American Left. In the process Cuban leaders departed from Marxist−Leninist orthodoxy, garnering harsh criticism from their Soviet and Chinese allies. Yet Cuba found a steadfast supporter of its controversial positions in North Korea. This support can in large part be explained by the parallels between Cuban and North Korean ideas about revolution in the developing nations of the Global South. Most significantly, both parties embraced a radical reconceptualisation of the role of the Marxist−Leninist vanguard party. This new doctrine appealed primarily to younger Latin American militants frustrated with the established leftist parties and party politics in general. The Cuban/North Korean theory of the party had a tangible influence in Colombia, Peru, Brazil, Puerto Rico, El Salvador, Mexico, Bolivia and Nicaragua, as revolutionary groups in these societies took up arms in the 1960s and 1970s.
White matter, cognition and psychotic-like experiences in UK Biobank
Authors: Bosma M. J. , Cox S. R. , Ziermans T. , Buchanan C. R. , Shen X. , Tucker-Drob E. M. , Adams M. J. , Whalley H. C. , Lawrie S. M.
Published: November 2021

Background

Psychotic-like experiences (PLEs) are risk factors for the development of psychiatric conditions like schizophrenia, particularly if associated with distress. As PLEs have been related to alterations in both white matter and cognition, we investigated whether cognition (g-factor and processing speed) mediates the relationship between white matter and PLEs.

Methods

We investigated two independent samples (6170 and 19 891) from the UK Biobank, through path analysis. For both samples, measures of whole-brain fractional anisotropy (gFA) and mean diffusivity (gMD), as indications of white matter microstructure, were derived from probabilistic tractography. For the smaller sample, variables whole-brain white matter network efficiency and microstructure were also derived from structural connectome data.

Results

The mediation of cognition on the relationships between white matter properties and PLEs was non-significant. However, lower gFA was associated with having PLEs in combination with distress in the full available sample (standardizedβ= −0.053,p= 0.011). Additionally, lower gFA/higher gMD was associated with lower g-factor (standardizedβ= 0.049,p< 0.001; standardizedβ= −0.027,p= 0.003), and partially mediated by processing speed with a proportion mediated of 7% (p= < 0.001) for gFA and 11% (p< 0.001) for gMD.

Conclusions

We show that lower global white matter microstructure is associated with having PLEs in combination with distress, which suggests a direction of future research that could help clarify how and why individuals progress from subclinical to clinical psychotic symptoms. Furthermore, we replicated that processing speed mediates the relationship between white matter microstructure and g-factor.
Testing the consequences of alcohol, cannabis, and nicotine use on hippocampal volume: a quasi-experimental cotwin control analysis of young adult twins
Authors: Harper Jeremy , Wilson Sylia , Bair Jessica L. , Hunt Ruskin H. , Thomas Kathleen M. , Malone Stephen M. , Iacono William G.
Published: November 2021

Background

Alcohol, cannabis, and nicotine use are highly comorbid and alarmingly prevalent in young adults. The hippocampus may be particularly sensitive to substance exposure. This remains largely untested in humans and familial risk may confound exposure effects. We extend prior work on alcohol and hippocampal volume in women by testing common and unique substance use effects and the potential moderating role of sex on hippocampal volume during emerging adulthood. A quasi-experimental cotwin control (CTC) design was used to separate familial risk from exposure consequences.

Methods

In a population-based sample of 435 24-year-old same-sex twins (58% women), dimensional measures (e.g. frequency, amount) of alcohol, cannabis, and nicotine use across emerging adulthood were assessed. Hippocampal volume was assessed using MRI.

Results

Greater substance use was significantly associated with lower hippocampal volume for women but not men. The same pattern was observed for alcohol, cannabis, and nicotine. CTC analyses provided evidence that hippocampal effects likely reflected familial risk and the consequence of substance use in general and alcohol and nicotine in particular; cannabis effects were in the expected direction but not significant. Within-pair mediation analyses suggested that the effect of alcohol use on the hippocampus may reflect, in part, comorbid nicotine use.

Conclusions

The observed hippocampal volume deviations in women likely reflected substance-related premorbid familial risk and the consequences of smoking and, to a lesser degree, drinking. Findings contribute to a growing body of work suggesting heightened risk among women toward experiencing deleterious effects of substance exposure on the still-developing young adult hippocampus.
Translanguaging in education
Authors: Bonacina-Pugh Florence , da Costa Cabral Ildegrada , Huang Jing
Published: November 2021

This state-of-the-art review focuses on translanguaging in education. In recent years, scholars have engaged in the conceptualisation of ‘translanguaging’ (e.g. García, 2009; García & Wei, 2014a; Wei, 2018) as well as in conducting a vast and ever-increasing number of empirical studies, in educational contexts in particular. This article aims to take stock of the different ways in which ‘translanguaging’ has been conceptualised and of the ways in which it has been interpreted and applied in the study of multilingualism in diverse educational contexts across the globe. Our review exercise shows that ‘translanguaging’ has been conceptualised within two different approaches, which we propose to call the ‘fixed language approach’ and the ‘fluid languaging approach’. It further shows how ‘translanguaging’ has been studied within these two approaches in different educational contexts. We finish our review by calling for new methodologies adapted to a linguistics of fluidity and by considering critically translanguaging as a scholarly phenomenon.
Reflections on a Career in Marine Geoscience
Authors: Watts A. B.
Published: November 2021

I began my career in the late 1960s at a time when some major oceanographic institutions were running upwards of 30 cruises a year. By the early 1980s, changes in funding patterns, satellite remote sensing, and “law of the sea” had started to impact ocean exploration. Nevertheless, technological advances, especially in sonar and seismic systems, have led to new discoveries on seafloor processes and underlying structures. Today, marine geoscience plays a pivotal role in Earth system science through projects such as Seabed 2030, International Ocean Drilling (IODP), and seismic imaging of mantle lithosphere, each of which pose opportunities and new challenges for the next generation.
Changes in Pore Geometry and Connectivity in the Basalt Pore Network Adjacent to Fractures in Response to CO2‐Saturated Fluid
Authors: Phukan Meghalim , Jyoti Apoorv , Black Jay R. , Haese Ralf R.
Published: November 2021

Pores connected to fractures provide an increased surface area for fluid‐rock interactions when reactive fluids, such as CO2‐saturated water, flow within fractures. Diffusion‐controlled transport of ions including dissolved CO2, Ca2+, Mg2+, Fe2+, and Si within the connected pore network can lead to local mineral undersaturation or supersaturation and respective local dissolution or precipitation of secondary minerals. In this study, a diffusion‐controlled experiment was conducted on a fractured basalt under subsurface conditions (60°C and 80 bars) to investigate the changes in the pore volume, the connectivity within the pore network, the pore and throat size distribution and to quantify the volume of dissolved and precipitated mineral phases. CO2‐saturated water with a supply of ions from the dissolution of basalt powder was reacted with an artificially fractured basalt sample over 12 weeks. The net pore volume of the sample decreased by 158 mm3, equivalent to 7.7% of the initial pore volume (2,041 mm3). The number of pores decreased considerably (15%) while the decline in the number of throats was small (4%) suggesting precipitation primarily occurred in pores. The number of isolated pores declined, which is attributed to mineral dissolution leading to greater connectivity within the pore network. Overall, the results provide insights into the early phase of reactive fluid flow in fractured basalt eventually leading to self‐sealing of fractures and the adjacent pore network.
TMEM116 is required for lung cancer cell motility and metastasis through PDK1 signaling pathway
Authors: Zhang Suhong , Dai Haiting , Li Wenya , Wang Runming , Wu Hanyu , Shen Ming , Hu Ye , Xie Lixin , Xing Yiming
Published: November 2021

Transmembrane protein (TMEM) is a family of protein that spans cytoplasmic membranes and allows cell–cell and cell–environment communication. Dysregulation of TMEMs has been observed in multiple cancers. However, little is known about TMEM116 in cancer development. In this study, we demonstrate that TMEM116 is highly expressed in non-small-cell lung cancer (NSCLC) tissues and cell lines. Inactivation of TMEM116 reduced cell proliferation, migration and invasiveness of human cancer cells and suppressed A549 induced tumor metastasis in mouse lungs. In addition, TMEM116 deficiency inhibited PDK1-AKT-FOXO3A signaling pathway, resulting in accumulation of TAp63, while activation of PDK1 largely reversed the TMEM116 deficiency induced defects in cancer cell motility, migration and invasive. Together, these results demonstrate that TMEM116 is a critical integrator of oncogenic signaling in cancer metastasis.
P2X7 promotes metastatic spreading and triggers release of miRNA-containing exosomes and microvesicles from melanoma cells
Authors: Pegoraro Anna , De Marchi Elena , Ferracin Manuela , Orioli Elisa , Zanoni Michele , Bassi Cristian , Tesei Anna , Capece Marina , Dika Emi , Negrini Massimo , Di Virgilio Francesco , Adinolfi Elena
Published: November 2021

Tumor growth and metastatic spreading are heavily affected by the P2X7 receptor as well as microvesicles and exosomes release into the tumor microenvironment. P2X7 receptor stimulation is known to trigger vesicular release from immune and central nervous system cells. However, P2X7 role in microvesicles and exosomes delivery from tumor cells was never analyzed in depth. Here we show that P2X7 is overexpressed in patients affected by metastatic malignant melanoma and that its expression closely correlates with reduced overall survival. Antagonism of melanoma cell-expressed P2X7 receptor inhibited in vitro anchorage-independent growth and migration and in vivo dissemination and lung metastasis formation. P2X7 stimulation triggered the release of miRNA-containing microvesicles and exosomes from melanoma cells, profoundly altering the nature of their miRNA content, as well as their dimensions and quantity. Among the more than 200 miRNAs that we found up-or-down-modulated for each vesicular fraction tested, we identified three miRNAs, miR-495-3p, miR-376c-3p, and miR-6730-3p, that were enriched in both the exosome and microvesicle fraction in a P2X7-dependent fashion. Interestingly, upon transfection, these miRNAs promoted melanoma cell growth or migration, and their vesicular release was minimized by P2X7 antagonism. Our data unveil an exosome/microvesicle and miRNA-dependent mechanism for the pro-metastatic activity of the P2X7 receptor and highlight this receptor as a suitable prognostic biomarker and therapeutic target in malignant melanoma.
Disulfide-compatible phage-assisted continuous evolution in the periplasmic space
Authors: Morrison Mary S. , Wang Tina , Raguram Aditya , Hemez Colin , Liu David R.
Published: November 2021

The directed evolution of antibodies has yielded important research tools and human therapeutics. The dependence of many antibodies on disulfide bonds for stability has limited the application of continuous evolution technologies to antibodies and other disulfide-containing proteins. Here we describe periplasmic phage-assisted continuous evolution (pPACE), a system for continuous evolution of protein-protein interactions in the disulfide-compatible environment of the E. coli periplasm. We first apply pPACE to rapidly evolve novel noncovalent and covalent interactions between subunits of homodimeric YibK protein and to correct a binding-defective mutant of the anti-GCN4 Ω-graft antibody. We develop an intein-mediated system to select for soluble periplasmic expression in pPACE, leading to an eight-fold increase in soluble expression of the Ω-graft antibody. Finally, we evolve disulfide-containing trastuzumab antibody variants with improved binding to a Her2-like peptide and improved soluble expression. Together, these results demonstrate that pPACE can rapidly optimize proteins containing disulfide bonds, broadening the applicability of continuous evolution.
Spontaneous exciton dissociation enables spin state interconversion in delayed fluorescence organic semiconductors
Authors: Gillett Alexander J. , Tonnelé Claire , Londi Giacomo , Ricci Gaetano , Catherin Manon , Unson Darcy M. L. , Casanova David , Castet Frédéric , Olivier Yoann , Chen Weimin M. , Zaborova Elena , Evans Emrys W. , Drummond Bluebell H. , Conaghan Patrick J. , Cui Lin-Song , Greenham Neil C. , Puttisong Yuttapoom , Fages Frédéric , Beljonne David , Friend Richard H.
Published: November 2021

Engineering a low singlet-triplet energy gap (ΔEST) is necessary for efficient reverse intersystem crossing (rISC) in delayed fluorescence (DF) organic semiconductors but results in a small radiative rate that limits performance in LEDs. Here, we study a model DF material, BF2, that exhibits a strong optical absorption (absorption coefficient = 3.8 × 105 cm−1) and a relatively large ΔEST of 0.2 eV. In isolated BF2 molecules, intramolecular rISC is slow (delayed lifetime = 260 μs), but in aggregated films, BF2 generates intermolecular charge transfer (inter-CT) states on picosecond timescales. In contrast to the microsecond intramolecular rISC that is promoted by spin-orbit interactions in most isolated DF molecules, photoluminescence-detected magnetic resonance shows that these inter-CT states undergo rISC mediated by hyperfine interactions on a ~24 ns timescale and have an average electron-hole separation of ≥1.5 nm. Transfer back to the emissive singlet exciton then enables efficient DF and LED operation. Thus, access to these inter-CT states, which is possible even at low BF2 doping concentrations of 4 wt%, resolves the conflicting requirements of fast radiative emission and low ΔEST in organic DF emitters.
A distributed fMRI-based signature for the subjective experience of fear
Authors: Zhou Feng , Zhao Weihua , Qi Ziyu , Geng Yayuan , Yao Shuxia , Kendrick Keith M. , Wager Tor D. , Becker Benjamin
Published: November 2021

The specific neural systems underlying the subjective feeling of fear are debated in affective neuroscience. Here, we combine functional MRI with machine learning to identify and evaluate a sensitive and generalizable neural signature predictive of the momentary self-reported subjective fear experience across discovery (n = 67), validation (n = 20) and generalization (n = 31) cohorts. We systematically demonstrate that accurate fear prediction crucially requires distributed brain systems, with important contributions from cortical (e.g., prefrontal, midcingulate and insular cortices) and subcortical (e.g., thalamus, periaqueductal gray, basal forebrain and amygdala) regions. We further demonstrate that the neural representation of subjective fear is distinguishable from the representation of conditioned threat and general negative affect. Overall, our findings suggest that subjective fear, which exhibits distinct neural representation with some other aversive states, is encoded in distributed systems rather than isolated ‘fear centers’.
The APPL1-Rab5 axis restricts NLRP3 inflammasome activation through early endosomal-dependent mitophagy in macrophages
Authors: Wu Kelvin Ka Lok , Long KeKao , Lin Huige , Siu Parco Ming Fai , Hoo Ruby Lai Chong , Ye Dewei , Xu Aimin , Cheng Kenneth King Yip
Published: November 2021

Although mitophagy is known to restrict NLRP3 inflammasome activation, the underlying regulatory mechanism remains poorly characterized. Here we describe a type of early endosome-dependent mitophagy that limits NLRP3 inflammasome activation. Deletion of the endosomal adaptor protein APPL1 impairs mitophagy, leading to accumulation of damaged mitochondria producing reactive oxygen species (ROS) and oxidized cytosolic mitochondrial DNA, which in turn trigger NLRP3 inflammasome overactivation in macrophages. NLRP3 agonist causes APPL1 to translocate from early endosomes to mitochondria, where it interacts with Rab5 to facilitate endosomal-mediated mitophagy. Mice deficient for APPL1 specifically in hematopoietic cell are more sensitive to endotoxin-induced sepsis, obesity-induced inflammation and glucose dysregulation. These are associated with increased expression of systemic interleukin-1β, a major product of NLRP3 inflammasome activation. Our findings indicate that the early endosomal machinery is essential to repress NLRP3 inflammasome hyperactivation by promoting mitophagy in macrophages.
RNF19A-mediated ubiquitination of BARD1 prevents BRCA1/BARD1-dependent homologous recombination
Authors: Zhu Qian , Huang Jinzhou , Huang Hongyang , Li Huan , Yi Peiqiang , Kloeber Jake A. , Yuan Jian , Chen Yuping , Deng Min , Luo Kuntian , Gao Ming , Guo Guijie , Tu Xinyi , Yin Ping , Zhang Yong , Su Jun , Chen Jiayi , Lou Zhenkun
Published: November 2021

BRCA1-BARD1 heterodimers act in multiple steps during homologous recombination (HR) to ensure the prompt repair of DNA double strand breaks. Dysfunction of the BRCA1 pathway enhances the therapeutic efficiency of poly-(ADP-ribose) polymerase inhibitors (PARPi) in cancers, but the molecular mechanisms underlying this sensitization to PARPi are not fully understood. Here, we show that cancer cell sensitivity to PARPi is promoted by the ring between ring fingers (RBR) protein RNF19A. We demonstrate that RNF19A suppresses HR by ubiquitinating BARD1, which leads to dissociation of BRCA1-BARD1 complex and exposure of a nuclear export sequence in BARD1 that is otherwise masked by BRCA1, resulting in the export of BARD1 to the cytoplasm. We provide evidence that high RNF19A expression in breast cancer compromises HR and increases sensitivity to PARPi. We propose that RNF19A modulates the cancer cell response to PARPi by negatively regulating the BRCA1-BARD1 complex and inhibiting HR-mediated DNA repair.
Seismic velocity structure of Unzen Volcano, Japan, and relationship to the magma ascent route during eruptions in 1990–1995
Authors: Miyano Kanta , Aizawa Koki , Matsushima Takeshi , Shito Azusa , Shimizu Hiroshi
Published: November 2021

Subsurface structures may control the migration of magma beneath a volcano. We used high-resolution seismic tomography to image a low- P-wave velocity (Vp) zone beneath Unzen Volcano, Japan, at depths of 3–16 km beneath sea level. The top of this low-Vp zone is located beneath Mt. Fugendake of Unzen volcano, which emitted 0.21 km3 of dacitic magma as lava domes and pyroclastic flows during eruptions in 1990–1995. Based on hypocenter migrations prior to the 1990–1995 eruptions and modeled pressure source locations for recorded crustal deformation, we conclude that the magma for the 1990–1995 eruptions migrated obliquely upward along the top of the low-Vp zone. As tectonic earthquakes occurred above the deeper part of the low-Vp zone, the deep low-Vp zone is interpreted to be a high-temperature region (> 400 °C) overlying the brittle–ductile transition. By further considering Vs and Vp/Vs structures, we suggest that the deeper part of the low-Vp zone constitutes a highly crystalized magma-mush reservoir, and the shallower part a volatile-rich zone.
Mental rotation ability predicts the acquisition of basic endovascular skills
Authors: Paul Katja I. , Glathe Annegret , Taatgen Niels A. , Steele Christopher J. , Villringer Arno , Lanzer Peter , Cnossen Fokie
Published: November 2021

Due to the increasing complexity of diseases in the aging population and rapid progress in catheter-based technology, the demands on operators’ skills in conducting endovascular interventions (EI) has increased dramatically, putting more emphasis on training. However, it is not well understood which factors influence learning and performance. In the present study, we examined the ability of EI naïve medical students to acquire basic catheter skills and the role of pre-existing cognitive ability and manual dexterity in predicting performance. Nineteen medical students practised an internal carotid artery angiography during a three-day training on an endovascular simulator. Prior to the training they completed a battery of tests. Skill acquisition was assessed using quantitative and clinical performance measures; the outcome measures from the test battery were used to predict the learning rate. The quantitative metrics indicated that participants’ performance improved significantly across the training, but the clinical evaluation revealed that participants did not significantly improve on the more complex part of the procedure. Mental rotation ability (MRA) predicted quantitative, but not clinical performance. We suggest that MRA tests in combination with simulator sessions could be used to assess the trainee’s early competence level and tailor the training to individual needs.
Spatiotemporal dynamics of a glioma immune interaction model
Authors: Khajanchi Subhas , Nieto Juan J.
Published: November 2021

We report a mathematical model which depicts the spatiotemporal dynamics of glioma cells, macrophages, cytotoxic-T-lymphocytes, immuno-suppressive cytokine TGF-β and immuno-stimulatory cytokine IFN-γ through a system of five coupled reaction-diffusion equations. We performed local stability analysis of the biologically based mathematical model for the growth of glioma cell population and their environment. The presented stability analysis of the model system demonstrates that the temporally stable positive interior steady state remains stable under the small inhomogeneous spatiotemporal perturbations. The irregular spatiotemporal dynamics of gliomas, macrophages and cytotoxic T-lymphocytes are discussed extensively and some numerical simulations are presented. Performed some numerical simulations in both one and two dimensional spaces. The occurrence of heterogeneous pattern formation of the system has both biological and mathematical implications and the concepts of glioma cell progression and invasion are considered. Simulation of the model shows that by increasing the value of time, the glioma cell population, macrophages and cytotoxic-T-lymphocytes spread throughout the domain.
Volumetric MRI is a promising outcome measure of muscle reinnervation
Authors: Wilcox Matthew , Dos Santos Canas Liane , Hargunani Rikin , Tidswell Tom , Brown Hazel , Modat Marc , Phillips James B. , Ourselin Sebastien , Quick Tom
Published: November 2021

The development of outcome measures that can track the recovery of reinnervated muscle would benefit the clinical investigation of new therapies which hope to enhance peripheral nerve repair. The primary objective of this study was to assess the validity of volumetric Magnetic Resonance Imaging (MRI) as an outcome measure of muscle reinnervation by testing its reproducibility, responsiveness and relationship with clinical indices of muscular function. Over a 3-year period 25 patients who underwent nerve transfer to reinnervate elbow flexor muscles were assessed using intramuscular electromyography (EMG) and MRI (median post-operative assessment time of 258 days, ranging from 86 days pre-operatively to 1698 days post- operatively). Muscle power (Medical Research Council (MRC) grade) and Stanmore Percentage of Normal Elbow Assessment (SPONEA) assessment was also recorded for all patients. Sub-analysis of peak volitional force (PVF), muscular fatigue and co-contraction was performed in those patients with MRC > 3. The responsiveness of each parameter was compared using Pearson or Spearman correlation. A Hierarchical Gaussian Process (HGP) was implemented to determine the ability of volumetric MRI measurements to predict the recovery of muscular function. Reinnervated muscle volume per unit Body Mass Index (BMI) demonstrated good responsiveness (R2 = 0.73, p < 0.001). Using the temporal and muscle volume per unit BMI data, a HGP model was able to predict MRC grade and SPONEA with a mean absolute error (MAE) of 0.73 and 1.7 respectively. Muscle volume per unit BMI demonstrated moderate to good positive correlations with patient reported impairments of reinnervated muscle; co- contraction (R2 = 0.63, p = 0.02) and muscle fatigue (R2 = 0.64, p = 0.04). In summary, volumetric MRI analysis of reinnervated muscle is highly reproducible, responsive to post-operative time and demonstrates correlation with clinical indices of muscle function. This encourages the view that volumetric MRI is a promising outcome measure for muscle reinnervation which will drive advancements in motor recovery therapy.
The transverse and longitudinal elastic constants of pulp fibers in paper sheets
Authors: Czibula Caterina , Brandberg August , Cordill Megan J. , Matković Aleksandar , Glushko Oleksandr , Czibula Chiara , Kulachenko Artem , Teichert Christian , Hirn Ulrich
Published: November 2021

Cellulose fibers are a major industrial input, but due to their irregular shape and anisotropic material response, accurate material characterization is difficult. Single fiber tensile testing is the most popular way to estimate the material properties of individual fibers. However, such tests can only be performed along the axis of the fiber and are associated with problems of enforcing restraints. Alternative indirect approaches, such as micro-mechanical modeling, can help but yield results that are not fully decoupled from the model assumptions. Here, we compare these methods with nanoindentation as a method to extract elastic material constants of the individual fibers. We show that both the longitudinal and the transverse elastic modulus can be determined, additionally enabling the measurement of fiber properties in-situ inside a sheet of paper such that the entire industrial process history is captured. The obtained longitudinal modulus is comparable to traditional methods for larger indents but with a strongly increased scatter as the size of the indentation is decreased further.