bluuebunny/crossref_metadata_2025 huggingface dataset:
Computing laminar boundary layers with the von Mises equation
Authors: Mills R. D. , Abedin M. Z.
Published: March 2023

There is much current interest in numerical methods of solution of the laminar boundary-layer equations. Methods used to date may generally be classified as

(i) explicit finite-difference methods (e.g. Refs. 1, 2, 3);

(ii) implicit finite-difference methods (e.g. Refs. 4, 5, 6, 7);

(iii) difference-differential methods (e.g. Ref. 8).

A method based on converting the boundary-layer problem into an integral equation and solving the latter by iteration has been developed by one of the present authors.
Pure bending of beams having initial curvature
Authors: Holland M.
Published: March 2023

Three theories of bending are available to the designer for the determination of bending stresses in curved beams. (1) The Euler-Bernoulli hypothesis (often referred to as the simple theory of bending), which assumes a linear distribution of bending stress, having a zero stress value at the mid-plane, i.e. the centroidal and neutral axes are coincident. (2) The Winkler theory, which predicts a depression of the neutral axis away from the centroidal axis and towards the centre of curvature. This theory produces a hyperbolic distribution of bending stress across the section, having a maximum amplitude at the fibre nearest the centre of curvature. (3) The Golovin theory, which is exact.
Movement of a line vortex pair downstream of a circular cylinder in potential flow
Authors: Williams R. V. , Burrows F. M.
Published: March 2023

Foppl’s stability analysis (1913) of the equilibrium positions of a line vortex pair in the downstream neighbourhood of a circular cylinder in the two-dimensional potential flow of an incompressible fluid moving with uniform speed at infinity has been corrected recently by Smith (1973). Smith shows that it is only for small symmetric displacements from any one pair of points on the locus of possible rest positions which is known as the Foppl curve there is neutral spatial stability, all other displacements being unstable. This correction now makes the results of the stability analysis consistent with the work of Dolaptchiev and Sendov (1959) who determined the trajectories followed by such a vortex pair when constrained so as to move in a wholly symmetric motion. Dolaptchiev and Sendov obtained the analytical solution of the differential equations for the completely symmetric motion, but for motion other than symmetric no simple solutions of this sort appear to exist although the vortex trajectories for any case can be deduced numerically without difficulty.
The rotor and its future
Authors: Jones J. P.
Published: March 2023

When delivering a Memorial lecture it is customary to open with a tribute to the one who is remembered. But the substance of my lecture is the rotor which Cierva evolved 50 years ago and I hope to sufficiently recognise his contribution during the delivery. Therefore with your permission I will content myself now with marking my deep appreciation of the honour done me by your invitation.

An informed layman reading past papers on rotors and rotorcraft would form the impression that each achievement was only a fleeting gain. The autogyro was to give way to the helicopter, the helicopter to the compound helicopter and the compound to the convertible rotorcraft. The rotor itself, it was argued, is ideal for hovering but hopelessly inefficient in forward flight. Hence the haste to get back to wings, a tendency much increased when fixed wing designers discovered how to use small, heavily loaded, rotors. But such is the lure of the rotor that even its detractors saw the case for its use in landing and take-off.
International airlines in a changing world
Authors: Shaw R. R.
Published: March 2023

It is a great honour and pleasure to be invited to deliver this Lawrence Hargrave Memorial Lecture in my home town—particularly as it gives me a chance to pay tribute to a man whose contributions to the development of the science of flight are commonly overlooked and usually under-rated.

I can remember vividly Professor Stephens delivering the first of these Memorial Lectures in 1956. With his whimsical sense of humour he started in a rather unconventional way. Without any of the usual introductory words he flashed a portrait of Lawrence Hargrave on the screen and said “Well, there he is—a handsome fellow—what you can see of him.” In a sense these words sum up the theme of my lecture. I want to discuss some of the outstanding problems of the international airline industry—an industry whose handsome features are at present somewhat obscured by adversity.
The Islander
Authors: Britten F. R. J.
Published: March 2023

The Islander is extremely simple and has had few aerodynamic problems; the exception was a persistent elevator “buzz” in some aircraft which was annoying more than it was serious and the cause of which was never satisfactorily established, despite an investigation that took six to seven months and which included wind tunnel testing and elaborate flight instrumentation. It was eventually reduced to an acceptable level by improved detail engineering.

The NACA 23012 section that we use is not a popular section nowadays despite having a good CL max, low CMO and low CDO. Its main drawback is the abrupt stall it can give to a wing. The usual cure for this is to provide generous washout. We chose to confine our washout to the wing tip and, as no dihedral was necessary apart from the tips, we achieved a very simple rectangular box structure with no joints—both a stressman's and a production engineer's dream. It is not often that you can please them both.
Errors Due to Pulsation in Orifice Meters
Authors: Grimson J. , Hay N.
Published: March 2023

At the present time, the only established method of metering a pulsating fluid flow involves the installation of damping devices in the system between the source of pulsation and the flow meter to ensure that the flow through the meter is essentially steady. Such devices may comprise a combination of frictional and volumetric damping and the method by which the required degree of damping is determined makes use of the Hodgson criterion. In many systems, it is undesirable (or, at least, inconvenient) to have to incorporate this damping and, therefore, the more direct approach, involving the metering of flow which is actually pulsating, is of considerable practical interest.

In the present note, the various factors affecting the metering errors in pulsating flow are discussed in relation to the results of an experimental investigation into the pulsating flow of air through a number of standard orifice configurations.
A Third London Airport
Authors: Haines P. C.
Published: March 2023

This symposium is about Airports and Transport Aircraft and Interface problems. The best way to deal with interface problems is not to have them.

My paper is about some of the interface problems which may arise concerning a Third London Airport if we do not plan them away beforehand. The majority of the points I shall be raising were identified during our work for the Commission on the Third London Airport and are fully set out in the Report on the Commission's Proceedings Papers and Proceedings Volume VIII Part 2, Section 2, to which you should turn for more detail.
A Note on Subsonic Linearised Theory for Symmetrical Cranked Wings at Zero Incidence
Authors: Lock R. C.
Published: March 2023

Research is in progress to assess, and if possible improve, the accuracy of a widely-used method for calculating the pressure distribution on swept wings in subsonic attached (inviscid) flow. Ref. 1 does not make specific recommendations on how to deal with wings having “cranked” planforms (i.e. wings with discontinuous changes in the sweep angle of the leading or trailing edges, other than at the central “kink” fundamental to the swept wing concept); but it implies (section 8.3) that the method of ref. 2 could be used for this purpose. A re-examination of this problem, in connection with the programme of work of the Transonic Aerodynamics Committee of the Royal Aeronautical Society, has revealed errors, which could be seriously misleading, in that part of ref. 2 dealing with the thickness effect. The object of the present note is to present the corrected formulae for the basic streamwise and span-wise components of perturbation velocity due to the thickness, at and near the crank, in the simplified example consisting of two semi-infinite wing panels of different sweep angles joined together; to examine the possible singularities in the flow field in the neighbourhood of the crank; and finally to discuss qualitatively the implications of these formulae on the magnitude of the “crank effect”, including the influence of free-stream Mach number.
Titanium Structures in Practice
Authors: Eccles D. , Heath W. G.
Published: March 2023

Developments in the technology have caused a steady decrease in the cost of introducing titanium into aircraft structures. This encouraging state of affairs has resulted in an increased use of titanium alloys, especially in the USA, where the development of supersonic aircraft has provided a prima facie case for their introduction.

In the UK the technology has not developed so rapidly, although both civil and military aircraft have gradually introduced more and more titanium components, principally forgings (see Fig. 1). Some years ago, however, it became apparent that the British aerospace industry could not afford either the time or the money involved in developing the technology for a specific new project. On the other hand, a new project without a substantial percentage of titanium in its structure could well be less efficient than a competitor featuring a large number of titanium components.
On the correction of hot wire turbulence measurements for spatial resolution errors
Authors: Roberts J. B.
Published: March 2023

Hot wire anemometers have found widespread use in the measurement of turbulence for many years. Recently, considerable improvements in the signal to noise ratio of these instruments has facilitated measurements in the high wavenumber region of the energy spectrum, where the turbulent energy level is usually relatively low.

Of major concern in the measurement of very small scale turbulent fluctuations by the hot wire method is the error introduced by the spatial averaging effect of the wire. Clearly, for fluctuations with wavelengths of the same order of magnitude as the wire length, or less, the line integration of the wire results in measured amplitudes which deviate considerably from those which would be recorded by a probe of infinitely small size.
On problems of flight over an extended angle-of-attack range
Authors: Thomas H. H. B. M.
Published: March 2023

To ensure successful operation of aircraft at high angles of attack (or high lift) conditions, attention must be paid to two basic design aims. These are the ability to achieve an adequate high lift performance and the need to ascertain that inadvertent penetration of the post-stall regime (or more generally any critical condition, which may for a particular aircraft be considered as replacing the conventional stall) does not lead to uncontrollable and thus potentially dangerous flight conditions.

The first aim is concerned primarily with the maintenance of the flow pattern associated with the normal flight regime and the augmentation of the lifting capability of the wings to sufficiently high lift coefficients. It, therefore, relates to the design of the wings, leading-edge devices and the flap system, if any, in respect of the onset of the flow breakdown.
A CONJECTURE OF MERCA ON CONGRUENCES MODULO POWERS OF 2 FOR PARTITIONS INTO DISTINCT PARTS
Authors: DU JULIA Q. D. , TANG DAZHAO
Published: March 2023

Let
$Q(n)$
denote the number of partitions of n into distinct parts. Merca [‘Ramanujan-type congruences modulo 4 for partitions into distinct parts’, An. Şt. Univ. Ovidius Constanţa30(3) (2022), 185–199] derived some congruences modulo
$4$
and
$8$
for
$Q(n)$
and posed a conjecture on congruences modulo powers of
$2$
enjoyed by
$Q(n)$
. We present an approach which can be used to prove a family of internal congruence relations modulo powers of
$2$
concerning
$Q(n)$
. As an immediate consequence, we not only prove Merca’s conjecture, but also derive many internal congruences modulo powers of
$2$
satisfied by
$Q(n)$
. Moreover, we establish an infinite family of congruence relations modulo
$4$
for
$Q(n)$
.
External Threats, Capacity, and Repression: How the Threat of War Affects Political Development and Physical Integrity Rights
Authors: Artabe Eugenia , Chapa Samantha , Sparkman Leah , Shea Patrick E.
Published: March 2023

How do external threats affect leaders' incentives to repress? We argue that external threats both increase and decrease state repression, but through different causal pathways. Directly, external threats provide leaders with political cover to use repression against political opponents. Indirectly, threats incentivize leaders to augment state capacity, which decreases the likelihood of state repression. To test this argument, we develop a new latent measure of external threat using a Bayesian measurement model. We use mediation analysis to examine the direct and indirect effects of external threats on repression in developing countries from 1980 to 2016. We find that external threats increase government repression directly, but indirectly decrease repression through stronger state capacity. Our findings have implications for how international factors connect to domestic politics to help explain state repression. In addition, our new measure of external threat will help scholars study the consequences of the international threat environment.
Serum neurofilament light concentrations are associated with cortical thinning in anorexia nervosa
Authors: Hellerhoff Inger , Bernardoni Fabio , Bahnsen Klaas , King Joseph A. , Doose Arne , Pauligk Sophie , Tam Friederike I. , Mannigel Merle , Gramatke Katrin , Roessner Veit , Akgün Katja , Ziemssen Tjalf , Ehrlich Stefan
Published: March 2023

Background

Anorexia nervosa (AN) is characterized by severe emaciation and drastic reductions of brain mass, but the underlying mechanisms remain unclear. The present study investigated the putative association between the serum-based protein markers of brain damage neurofilament light (NF-L), tau protein, and glial fibrillary acidic protein (GFAP) and cortical thinning in acute AN.

Methods

Blood samples and magnetic resonance imaging scans were obtained from 52 predominantly adolescent, female patients with AN before and after partial weight restoration (increase in body mass index >14%). The effect of marker levels before weight gain and change in marker levels on cortical thickness (CT) was modeled at each vertex of the cortical surface using linear mixed-effect models. To test whether the observed effects were specific to AN, follow-up analyses exploring a potential general association of marker levels with CT were conducted in a female healthy control (HC) sample (n= 147).

Results

In AN, higher baseline levels of NF-L, an established marker of axonal damage, were associated with lower CT in several regions, with the most prominent clusters located in bilateral temporal lobes. Tau protein and GFAP were not associated with CT. In HC, no associations between damage marker levels and CT were detected.

Conclusions

A speculative interpretation would be that cortical thinning in acute AN might be at least partially a result of axonal damage processes. Further studies should thus test the potential of serum NF-L to become a reliable, low-cost and minimally invasive marker of structural brain alterations in AN.
Care for the Family and the Environment in China's Coal Country
Authors: Bruckermann Charlotte
Published: March 2023

In the “coal province” of Shanxi, residents grapple with tensions between caring for their families and caring about their environment. In creating ethical pathways through care, residents must navigate the paradox of livelihoods dependent on forms of development that endanger lives and pollute environments. This dilemma has crystallized over time, as the personal and particular demands of the present have become enmeshed with long-standing concerns over environmental degradation. Rather than characterizing family care as concrete and environmental care as abstract, acts of care in Shanxi link the reproductive crisis of the family with the reproductive crisis of the environment: the article presents instances under which the attention, empathy and recognition of care for concrete others are scaled up to the levels of ecology and planetary crisis.
Community perceptions of environmental water: a review
Authors: Kosovac Anna , Horne Avril C , O’Donnell Erin
Published: March 2023

Allocation of water specifically to the environment (often dubbed ‘environmental water’ or ‘environmental flows’) can be contentious within government, among irrigators and between community members. The reduction in supply of fresh water has led to questions surrounding the efficiencies and ecological value of securing these adequate flows for waterways. This literature review examines the evidence on these perceptions of environmental water allocations, focusing foremost on general public, irrigator, Indigenous and decision-maker perspectives. Existing studies are predominantly in Global North areas such as Australia, Canada and the USA. Two themes featured strongly in the papers: the importance of personal values in the acceptance of environmental water and the perception of fairness in environmental water allocation processes. Although the research area has been expanding, there is still limited representation in types of study, disciplinary backgrounds and study locations, and as such many research opportunities remain.
The Un-‘Common Sense’ of National Identity: Luigi Molina, Trentini and the Fascist Italianisation Campaign in Trentino-Alto Adige/Südtirol
Authors: McLean Eden K.
Published: March 2023

This article employs the recently discovered memoir of Luigi Molina – the superintendent of schools in Italy's multilingual borderland of Trentino-Alto Adige/Südtirol from 1923 to 1944 – to demonstrate the sizeable and problematic rift between purportedly ‘common-sense’ understandings of ‘Italian-ness’ (italianità) as they were manifested in Italy's newly annexed Alpine territory and in Rome. In particular, the author focuses on the state's treatment of the region's Italian speakers (trentini) in its attempts to ‘Italianise’ their German-speaking neighbours and solidify fascist control of Italy's northern border. Ultimately, Molina's recollections recount how Rome's struggles to articulate and implement clear and consistent criteria for Italianisation led to the weakening of regional officials’ moral authority, political support and ‘totalitarian’ façade. The simultaneously vague and critical project of Italianisation did not simply illuminate fascism's inability to inculcate an ‘Italian identity’ among Tyroleans, however; it also served to highlight fundamental difficulties in defining national identities in any nation-state.
Fiscal policy and the twin deficits: structural changes matter
Authors: Kim Wongi
Published: March 2023

This paper empirically and theoretically investigates the relationship between budget balances and external balances, the so-called twin deficit hypothesis. Using the US post-World War II data, I estimate a time-varying structural vector autoregressive model to evaluate the effects of structural breaks on this relationship. The empirical results reveal that the relationship is significantly time varying: (1) an increase in government spending and the consequent budget deficits tend to cause trade deficits in the Bretton Woods era; (2) in contrast, an increase in government spending tends to induce trade surpluses in the post-Bretton Woods era; and (3) with the exceptions of the 1980s and 2010s, government spending shocks cause trade deficits under a floating exchange regime. Using the open economy New Keynesian model with rule-of-thumb consumers, I find that a shift in exchange rate regimes helps in understanding empirical results (1) and (2). Moreover, slowly adjusted taxes inform our comprehension of exceptions in the 1980s, whereas zero lower bound aids our explanation of exceptions in the 2010s.
The challenges for health professionals delivering palliative care in the community during the COVID-19 pandemic: An integrative review
Authors: Frey Rosemary , Balmer Deborah
Published: March 2023

Objectives

The growing demand for palliative care has been accelerated due to the COVID-19 pandemic. However, providing community-based palliative care was also more difficult to do safely and faced several challenges. The goal of this integrative review was to identify, describe, and synthesize previous studies on the challenges for health professionals delivering palliative care in the community during the COVID-19 pandemic.

Methods

Searches were carried out on the Ovid MEDLINE, CINAHL, PsycINFO, Social Care Online, PubMed, Embase, and Expanded Academic databases. Journals typically reporting palliative care and community health studies were also searched (Palliative Medicine, Journal of Pain and Symptom Management, and Health & Social Care in the Community). All articles were peer-reviewed and published in English between December 2019 and September 2022.

Results

Database and hand searches identified 1231 articles. After duplicates were removed and the exclusion criteria applied, 27 articles were included in the final review. Themes in the research findings centered on 6 interconnected categories. The challenges imposed by the pandemic (lack of resources, communication difficulties, access to education and training, and interprofessional coordination), as well as the varying levels of success of the health-care responses, impacted the well-being of health professionals and, in turn, the well-being and care of patients and families.

Significance of results

The pandemic has provided the impetus for rethinking flexible and innovative approaches to overcome the challenges of delivering community palliative care. However, existing governmental and organizational policies require revision to improve communication and effective interprofessional collaboration, and additional resources are needed. A blended model of virtual and in-person palliative care delivery may provide the best solution to community palliative care delivery moving forward.
Okapi-EM: A napari plugin for processing and analyzing cryogenic serial focused ion beam/scanning electron microscopy images
Authors: Perdigão Luís M. A. , Ho Elaine M. L. , Cheng Zhiyuan C. , Yee Neville B.-Y. , Glen Thomas , Wu Liang , Grange Michael , Dumoux Maud , Basham Mark , Darrow Michele C.
Published: March 2023

An emergent volume electron microscopy technique called cryogenic serial plasma focused ion beam milling scanning electron microscopy (pFIB/SEM) can decipher complex biological structures by building a three-dimensional picture of biological samples at mesoscale resolution. This is achieved by collecting consecutive SEM images after successive rounds of FIB milling that expose a new surface after each milling step. Due to instrumental limitations, some image processing is necessary before 3D visualization and analysis of the data is possible. SEM images are affected by noise, drift, and charging effects, that can make precise 3D reconstruction of biological features difficult. This article presents Okapi-EM, an open-source napari plugin developed to process and analyze cryogenic serial pFIB/SEM images. Okapi-EM enables automated image registration of slices, evaluation of image quality metrics specific to pFIB-SEM imaging, and mitigation of charging artifacts. Implementation of Okapi-EM within the napari framework ensures that the tools are both user- and developer-friendly, through provision of a graphical user interface and access to Python programming.
Partizipationsmöglichkeiten von Kindern in gruppenpädagogischen Settings
Authors: Abeck Ina-Marie , Jegodtka Aljoscha , Schmude Corinna
Published: March 2023

Zusammenfassung. Partizipation ist ein wichtiges Element in der Umsetzung von Inklusion im Kita-Alltag, da dadurch Kindern Selbstbestimmung, Teilhabe und -gabe konkret ermöglicht wird ( Prengel, 2016 ; Wagner, 2012 ). Im Fokus der vorgestellten videografischen Studie steht der Morgenkreis als wiederkehrendes gruppenpädagogisches Setting und potenzieller Ort für demokratische Beteiligung im Kita-Alltag. Partizipation wird hier im Sinne von Beteiligung und Mitbestimmung von Kindern in Entscheidungsprozessen untersucht. In der Analyse zeigt sich, dass Mitbestimmung von Kindern im Morgenkreis bisher nur ansatzweise umgesetzt wird. Entscheidungssituationen werden selten von der Fachkraft gezielt für alle Kinder partizipativ gestaltet. Wenn Kinder an Entscheidungsprozessen mitwirken, haben diese tendenziell keine verbindliche Rolle bei der Entscheidungsfindung.
Mobilization and Export of Particulate and Dissolved Solids and Organic Carbon From Contrasting Mountainous River Watersheds in California and Oregon
Authors: Goñi Miguel A. , Welch Kylie A. , Ghazi Layla , Pett‐Ridge Julie C. , Haley Brian A.
Published: March 2023

Concentration‐discharge (C‐Q) relationships of total suspended solids (TSS), total dissolved solids (TDS), particulate organic carbon (POC), and dissolved organic carbon (DOC) were investigated in the tributaries and main‐stems of two mountainous river systems with distinct watershed characteristics (Eel and Umpqua rivers) in Northern California and central Oregon (USA). Power‐law (C = a × Qb) fits to the data showed strong transport‐limited behavior (b > 1) by TSS and POC, moderate transport limitation of DOC (b > 0.3) and chemostatic behavior (b < 0) by TDS in most streams. These contrasts led to significant compositional differences at varying discharge levels, with particle‐bound constituents becoming increasingly important (relative abundances of 50% to >90%) at high‐flow conditions. Organic carbon contents of TSS displayed marked decreases with discharge whereas they increased in TDS during high‐flow conditions. Daily and cumulative material fluxes for different coastal streams were calculated using the C‐Q relationships and showed that the delivery of transport‐limited constituents, such as TSS and POC (and DOC to a lesser degree), was closely tied to high‐discharge events and occurred primarily during the winter season. The coherence between winter fluxes and high wave‐southerly wind conditions along the coast highlights how seasonal and inter‐annual differences in fluvial discharge patterns affect the fate of land‐derived materials delivered to coastal regions.
Late‐Orogenic Evolution of the Southern European Variscan Belt Constrained by Fabric Analysis and Dating of the Camarat Granitic Complex and Coeval Felsic Dykes (Maures–Tanneron Massif, SE France)
Authors: Bolle Olivier , Corsini Michel , Diot Hervé , Laurent Oscar , Melis Raphaël
Published: March 2023

The Camarat Granitic Complex (CGC), emplaced in the migmatitic Internal Zone of the Maures–Tanneron Massif (MTM), SE Variscides, consists of the Gigaro granodiorite and the composite Camarat granite. U‐Pb dating of the latter gives crystallization ages of 304.5 ± 3.3 Ma (zircon date) and 303.5 ± 4.0 Ma (monazite date). Two representatives of late felsic dykes cutting across the MTM Internal Zone have 39Ar/40Ar muscovite ages of 302.43 ± 2.62 Ma and 298.11 ± 2.38. Magmatic lineations revealed by anisotropy of magnetic susceptibility (AMS) measurements and image analysis, aplite dykes, dyke‐like bodies of cordierite microgranite and joints in the Camarat granite, as well as the late dykes all have orientations consistent with subhorizontal, NNE‐SSW‐trending lineations in the migmatitic country rocks representing the stretching direction of a late‐Variscan transpression phase (D3). The CGC and the late dykes are therefore witness to a thermal event that affected the MTM between ∼305 and ∼298 Ma (late Pennsylvanian–earliest Permian times), at the end of D3 which initiated at ∼325 Ma. Grabens related to post‐Variscan, Permian rifting (D4 phase), which cut across the MTM are WNW‐ESE‐trending, indicating a NNE‐SSW direction of extension, parallel to the previous (D3) lateral horizontal flow. The present results and a comparison with AMS data published for the Corsica–Sardinia Batholith reveal that evolution in the SE Variscides from Devonian–early Carboniferous contraction to Permian extension, through late Carboniferous transpression is characterized by the persistence of a ca. N‐S stretching direction, supporting a strong horizontal, orogen‐parallel crustal flow.
Representation of Fully Three‐Dimensional Interfacial Curvature in Pore‐Network Models
Authors: Giudici Luke M. , Qaseminejad Raeini A. , Blunt Martin J. , Bijeljic Branko
Published: March 2023

Quasi two‐dimensional approximations of interfacial curvature, present in current network models of multiphase flow in porous media, are extended to three dimensions. The new expressions for threshold capillary pressure are validated and calibrated using high‐resolution direct numerical simulations on synthetic geometries. The effects of pore‐space expansion and sagittal interface curvature on displacement are quantified, and are shown to be a key step in improving the physical accuracy of network models. Finally, the calibrated network model is used to obtain predictions for relative permeability and capillary pressure in a water‐wet Bentheimer sandstone. The predictions are compared to experimental measurements, revealing that the inclusion of three‐dimensional interfacial curvature leads to more accurate predictions.
Altered behavior, brain structure, and neurometabolites in a rat model of autism-specific maternal autoantibody exposure
Authors: Bruce Matthew R. , Couch Amalie C. M. , Grant Simone , McLellan Janna , Ku Katherine , Chang Christina , Bachman Angelica , Matson Matthew , Berman Robert F. , Maddock Richard J. , Rowland Douglas , Kim Eugene , Ponzini Matthew D. , Harvey Danielle , Taylor Sandra L. , Vernon Anthony C. , Bauman Melissa D. , Van de Water Judy
Published: March 2023

Maternal immune dysregulation is a prenatal risk factor for autism spectrum disorder (ASD). Importantly, a clinically relevant connection exists between inflammation and metabolic stress that can result in aberrant cytokine signaling and autoimmunity. In this study we examined the potential for maternal autoantibodies (aAbs) to disrupt metabolic signaling and induce neuroanatomical changes in the brains of exposed offspring. To accomplish this, we developed a model of maternal aAb exposure in rats based on the clinical phenomenon of maternal autoantibody-related ASD (MAR-ASD). Following confirmation of aAb production in rat dams and antigen-specific immunoglobulin G (IgG) transfer to offspring, we assessed offspring behavior and brain structure longitudinally. MAR-ASD rat offspring displayed a reduction in pup ultrasonic vocalizations and a pronounced deficit in social play behavior when allowed to freely interact with a novel partner. Additionally, longitudinal in vivo structural magnetic resonance imaging (sMRI) at postnatal day 30 (PND30) and PND70, conducted in a separate cohort of animals, revealed sex-specific differences in total and regional brain volume. Treatment-specific effects by region appeared to converge on midbrain and cerebellar structures in MAR-ASD offspring. Simultaneously, in vivo 1H magnetic resonance spectroscopy (1H-MRS) data were collected to examine brain metabolite levels in the medial prefrontal cortex. Results showed that MAR-ASD offspring displayed decreased levels of choline-containing compounds and glutathione, accompanied by increased taurine compared to control animals. Overall, we found that rats exposed to MAR-ASD aAbs present with alterations in behavior, brain structure, and neurometabolites; reminiscent of findings observed in clinical ASD.
E2F1-mediated KDM4A-AS1 up-regulation promotes EMT of hepatocellular carcinoma cells by recruiting ILF3 to stabilize AURKA mRNA
Authors: Shen Hao-Ming , Zhang Di , Xiao Ping , Qu Bin , Sun Yi-Fan
Published: March 2023

Hepatocellular carcinoma (HCC) is a gastrointestinal tumor with high clinical incidence. Long non-coding RNAs (lncRNAs) play vital roles in modulating the growth and epithelial-mesenchymal transition (EMT) of HCC. However, the underlying mechanism of lncRNA KDM4A antisense RNA 1 (KDM4A-AS1) in HCC remains elusive. In our study, the role of KDM4A-AS1 in HCC was systematically investigated. The levels of KDM4A-AS1, interleukin enhancer-binding factor 3 (ILF3), Aurora kinase A (AURKA), and E2F transcription factor 1 (E2F1) were determined by RT-qPCR or western blot. ChIP and dual luciferase reporter experiments were performed to detect the binding relationship between E2F1 and KDM4A-AS1 promoter sequence. RIP and RNA-pull down confirmed the interaction of ILF3 with KDM4A-AS1/AURKA. Cellular functions were analyzed by MTT, flow cytometry, wound healing and transwell assays. IHC was performed to detect Ki67 in vivo. We found that KDM4A-AS1 was increased in HCC tissues and cells. Elevated KDM4A-AS1 level was correlated to poor prognosis of HCC. Knockdown of KDM4A-AS1 inhibited the proliferation, migration, invasion and EMT of HCC cells. ILF3 bound to KDM4A-AS1 and AURKA. KDM4A-AS1 maintained the stability of AURKA mRNA by recruiting ILF3. E2F1 transcriptionally activated KDM4A-AS1. Overexpressed KDM4A-AS1 reversed the contribution of E2F1 depletion to AURKA expression and EMT in HCC cells. KDM4A-AS1 promoted tumor formation in vivo through the PI3K/AKT pathway. These results revealed that E2F1 transcriptionally activated KDM4A-AS1 to regulate HCC progression via the PI3K/AKT pathway. E2F1 and KDM4A-AS1 may serve as good prognostic targets for HCC treatment.
Deletion of Gpatch2 does not alter Tnf expression in mice
Authors: Dalseno Destiny , Anderton Holly , Kueh Andrew , Herold Marco J , Silke John , Strasser Andreas , Bouillet Philippe
Published: March 2023

The cytokine TNF has essential roles in immune defence against diverse pathogens and, when its expression is deregulated, it can drive severe inflammatory disease. The control of TNF levels is therefore critical for normal functioning of the immune system and health. We have identified GPATCH2 as a putative repressor of Tnf expression acting post-transcriptionally through the TNF 3’ UTR in a CRISPR screen for novel regulators of TNF. GPATCH2 is a proposed cancer-testis antigen with roles reported in proliferation in cell lines. However, its role in vivo has not been established. We have generated Gpatch2−/− mice on a C57BL/6 background to assess the potential of GPATCH2 as a regulator of Tnf expression. Here we provide the first insights into Gpatch2−/− animals and show that loss of GPATCH2 affects neither basal Tnf expression in mice, nor Tnf expression in intraperitoneal LPS and subcutaneous SMAC-mimetic injection models of inflammation. We detected GPATCH2 protein in mouse testis and at lower levels in several other tissues, however, the morphology of the testis and these other tissues appears normal in Gpatch2−/− animals. Gpatch2−/− mice are viable, appear grossly normal, and we did not detect notable aberrations in lymphoid tissues or blood cell composition. Collectively, our results suggest no discernible role of GPATCH2 in Tnf expression, and the absence of an overt phenotype in Gpatch2−/− mice warrants further investigation of the role of GPATCH2.
Risk of death following COVID-19 vaccination or positive SARS-CoV-2 test in young people in England
Authors: Nafilyan Vahé , Bermingham Charlotte R. , Ward Isobel L. , Morgan Jasper , Zaccardi Francesco , Khunti Kamlesh , Stanborough Julie , Banerjee Amitava , Doidge James C.
Published: March 2023

Several studies have reported associations between COVID-19 vaccination and risk of cardiac diseases, especially in young people; the impact on mortality, however, remains unclear. We use national, linked electronic health data in England to assess the impact of COVID-19 vaccination and positive SARS-CoV-2 tests on the risk of cardiac and all-cause mortality in young people (12 to 29 years) using a self-controlled case series design. Here, we show there is no significant increase in cardiac or all-cause mortality in the 12 weeks following COVID-19 vaccination compared to more than 12 weeks after any dose. However, we find an increase in cardiac death in women after a first dose of non mRNA vaccines. A positive SARS-CoV-2 test is associated with increased cardiac and all-cause mortality among people vaccinated or unvaccinated at time of testing.
Ultrafast 3D nanofabrication via digital holography
Authors: Ouyang Wenqi , Xu Xiayi , Lu Wanping , Zhao Ni , Han Fei , Chen Shih-Chi
Published: March 2023

There has been a compelling demand of fabricating high-resolution complex three-dimensional (3D) structures in nanotechnology. While two-photon lithography (TPL) largely satisfies the need since its introduction, its low writing speed and high cost make it impractical for many large-scale applications. We report a digital holography-based TPL platform that realizes parallel printing with up to 2000 individually programmable laser foci to fabricate complex 3D structures with 90 nm resolution. This effectively improves the fabrication rate to 2,000,000 voxels/sec. The promising result is enabled by the polymerization kinetics under a low-repetition-rate regenerative laser amplifier, where the smallest features are defined via a single laser pulse at 1 kHz. We have fabricated large-scale metastructures and optical devices of up to centimeter-scale to validate the predicted writing speed, resolution, and cost. The results confirm our method provides an effective solution for scaling up TPL for applications beyond laboratory prototyping.
Conserved transcription factors promote cell fate stability and restrict reprogramming potential in differentiated cells
Authors: Missinato Maria A. , Murphy Sean , Lynott Michaela , Yu Michael S. , Kervadec Anaïs , Chang Yu-Ling , Kannan Suraj , Loreti Mafalda , Lee Christopher , Amatya Prashila , Tanaka Hiroshi , Huang Chun-Teng , Puri Pier Lorenzo , Kwon Chulan , Adams Peter D. , Qian Li , Sacco Alessandra , Andersen Peter , Colas Alexandre R.
Published: March 2023

Defining the mechanisms safeguarding cell fate identity in differentiated cells is crucial to improve 1) - our understanding of how differentiation is maintained in healthy tissues or altered in a disease state, and 2) - our ability to use cell fate reprogramming for regenerative purposes. Here, using a genome-wide transcription factor screen followed by validation steps in a variety of reprogramming assays (cardiac, neural and iPSC in fibroblasts and endothelial cells), we identified a set of four transcription factors (ATF7IP, JUNB, SP7, and ZNF207 [AJSZ]) that robustly opposes cell fate reprogramming in both lineage and cell type independent manners. Mechanistically, our integrated multi-omics approach (ChIP, ATAC and RNA-seq) revealed that AJSZ oppose cell fate reprogramming by 1) - maintaining chromatin enriched for reprogramming TF motifs in a closed state and 2) - downregulating genes required for reprogramming. Finally, KD of AJSZ in combination with MGT overexpression, significantly reduced scar size and improved heart function by 50%, as compared to MGT alone post-myocardial infarction. Collectively, our study suggests that inhibition of barrier to reprogramming mechanisms represents a promising therapeutic avenue to improve adult organ function post-injury.
An actin filament branching surveillance system regulates cell cycle progression, cytokinesis and primary ciliogenesis
Authors: Cao Muqing , Zou Xiaoxiao , Li Chaoyi , Lin Zaisheng , Wang Ni , Zou Zhongju , Ye Youqiong , Seemann Joachim , Levine Beth , Tang Zaiming , Zhong Qing
Published: March 2023

Dysfunction of cell cycle control and defects of primary ciliogenesis are two features of many cancers. Whether these events are interconnected and the driving mechanism coordinating them remains elusive. Here, we identify an actin filament branching surveillance system that alerts cells of actin branching insufficiency and regulates cell cycle progression, cytokinesis and primary ciliogenesis. We find that Oral-Facial-Digital syndrome 1 functions as a class II Nucleation promoting factor to promote Arp2/3 complex-mediated actin branching. Perturbation of actin branching promotes OFD1 degradation and inactivation via liquid-to-gel transition. Elimination of OFD1 or disruption of OFD1-Arp2/3 interaction drives proliferating, non-transformed cells into quiescence with ciliogenesis by an RB-dependent mechanism, while it leads oncogene-transformed/cancer cells to incomplete cytokinesis and irreversible mitotic catastrophe via actomyosin ring malformation. Inhibition of OFD1 leads to suppression of multiple cancer cell growth in mouse xenograft models. Thus, targeting OFD1-mediated actin filament branching surveillance system provides a direction for cancer therapy.
Single-molecule localization microscopy reveals the ultrastructural constitution of distal appendages in expanded mammalian centrioles
Authors: Chang Ting-Jui Ben , Hsu Jimmy Ching-Cheng , Yang T. Tony
Published: March 2023

Distal appendages (DAPs) are vital in cilia formation, mediating vesicular and ciliary docking to the plasma membrane during early ciliogenesis. Although numerous DAP proteins arranging a nine-fold symmetry have been studied using superresolution microscopy analyses, the extensive ultrastructural understanding of the DAP structure developing from the centriole wall remains elusive owing to insufficient resolution. Here, we proposed a pragmatic imaging strategy for two-color single-molecule localization microscopy of expanded mammalian DAP. Importantly, our imaging workflow enables us to push the resolution limit of a light microscope well close to a molecular level, thus achieving an unprecedented mapping resolution inside intact cells. Upon this workflow, we unravel the ultra-resolved higher-order protein complexes of the DAP and its associated proteins. Intriguingly, our images show that C2CD3, microtubule triplet, MNR, CEP90, OFD1, and ODF2 jointly constitute a unique molecular configuration at the DAP base. Moreover, our finding suggests that ODF2 plays an auxiliary role in coordinating and maintaining DAP nine-fold symmetry. Together, we develop an organelle-based drift correction protocol and a two-color solution with minimum crosstalk, allowing a robust localization microscopy imaging of expanded DAP structures deep into the gel-specimen composites.
Single cell analysis in head and neck cancer reveals potential immune evasion mechanisms during early metastasis
Authors: Quah Hong Sheng , Cao Elaine Yiqun , Suteja Lisda , Li Constance H. , Leong Hui Sun , Chong Fui Teen , Gupta Shilpi , Arcinas Camille , Ouyang John F. , Ang Vivian , Celhar Teja , Zhao Yunqian , Tay Hui Chen , Chan Jerry , Takahashi Takeshi , Tan Daniel S. W. , Biswas Subhra K. , Rackham Owen J. L. , Iyer N. Gopalakrishna
Published: March 2023

Profiling tumors at single-cell resolution provides an opportunity to understand complexities underpinning lymph-node metastases in head and neck squamous-cell carcinoma. Single-cell RNAseq (scRNAseq) analysis of cancer-cell trajectories identifies a subpopulation of pre-metastatic cells, driven by actionable pathways including AXL and AURK. Blocking these two proteins blunts tumor invasion in patient-derived cultures. Furthermore, scRNAseq analyses of tumor-infiltrating CD8 + T-lymphocytes show two distinct trajectories to T-cell dysfunction, corroborated by their clonal architecture based on single-cell T-cell receptor sequencing. By determining key modulators of these trajectories, followed by validation using external datasets and functional experiments, we uncover a role for SOX4 in mediating T-cell exhaustion. Finally, interactome analyses between pre-metastatic tumor cells and CD8 + T-lymphocytes uncover a putative role for the Midkine pathway in immune-modulation and this is confirmed by scRNAseq of tumors from humanized mice. Aside from specific findings, this study demonstrates the importance of tumor heterogeneity analyses in identifying key vulnerabilities during early metastasis.
Evanescent field trapping and propulsion of Janus particles along optical nanofibers
Authors: Tkachenko Georgiy , Truong Viet Giang , Esporlas Cindy Liza , Sanskriti Isha , Nic Chormaic Síle
Published: March 2023

Small composite objects, known as Janus particles, drive sustained scientific interest primarily targeted at biomedical applications, where such objects act as micro- or nanoscale actuators, carriers, or imaging agents. A major practical challenge is to develop effective methods for the manipulation of Janus particles. The available long-range methods mostly rely on chemical reactions or thermal gradients, therefore having limited precision and strong dependency on the content and properties of the carrier fluid. To tackle these limitations, we propose the manipulation of Janus particles (here, silica microspheres half-coated with gold) by optical forces in the evanescent field of an optical nanofiber. We find that Janus particles exhibit strong transverse localization on the nanofiber and much faster propulsion compared to all-dielectric particles of the same size. These results establish the effectiveness of near-field geometries for optical manipulation of composite particles, where new waveguide-based or plasmonic solutions could be envisaged.
Flexible and transparent thin-film light-scattering photovoltaics about fabrication and optimization for bifacial operation
Authors: Choi Soo-Won , Park Jae-Ho , Seo Ji-Woo , Mun Chaewon , Kim Yonghun , Song Pungkeun , Shin Myunghun , Kwon Jung-Dae
Published: March 2023

Flexible and transparent thin-film silicon solar cells were fabricated and optimized for building-integrated photovoltaics and bifacial operation. A laser lift-off method was developed to avoid thermal damage during the transfer of light-scattering structures onto colorless polyimide substrates and thus enhance front-incidence photocurrent, while a dual n-type rear window layer was introduced to reduce optical losses, facilitate electron transport for rear incidence, and thus enhance performance during bifacial operation. The introduction of the window layer increased the rear-to-front power conversion efficiency ratio to ~86%. The optimized bifacial power conversion efficiency for front and rear irradiances of 1 and 0.3 sun, respectively, equaled 6.15%, and the average transmittance within 500–800 nm equaled 36.9%. Additionally, the flexible and transparent solar cells fabricated using laser lift-off exhibited good mechanical reliability (i.e., sustained 500 cycles at a bending radius of 6 mm) and were therefore suitable for building-integrated photovoltaics.