bluuebunny/crossref_metadata_2025 huggingface dataset:
Holzer Method for Forced-Damped Torsional Vibrations
Authors: Spaetgens T. W.
Published: April 2021

The forced and resonant-vibration characteristics of a torsional system are easily enough determined by the well-known Holzer methods, in the case where the only major damping influences available in the system are those of the prime-mover itself, or of the propeller, in the case of a propeller-propulsion system. Where a damper exists within the system, the classic solution confines itself to the determination of the resonant-vibration characteristics under optimum damping conditions, and utilizes the principle of energy balance in conjunction with an equivalent system. The problem of forced vibration in a system having a damper is not susceptible, however, to such simple treatment regardless of whether or not the damping is optimum. This paper outlines an exact method, whereby both the forced- and the resonant-vibration characteristics of a viscously damped system may be calculated for any existing damping condition, optimum or otherwise, and which utilizes the ever-popular Holzer form.
On Plastic Flow and Vibrations
Authors: Thorne C. J.
Published: April 2021

A general solution is given for the behavior in the linear case of a mechanical model proposed and used by Henry Eyring and others. Four examples are worked in detail. In particular, the steady-state solution for the deflection in periodic vibrations is given in terms of the material constants for any frequency. The transients are given in detail for the three possible cases and inequalities are given to determine which case a particular problem is.
Flow of Heated Gases
Authors: Thompson A. S.
Published: April 2021

The purpose of this investigation was to find a convenient method for correlating the variables involved in the transfer of heat from the wall of a passage to a gas moving at high velocity in the passage. A graphical design method has been developed, using the Reynolds analogy between heat transfer and friction, for one-dimensional flow in a passage of variable area, and with variable wall temperature.
Some Experiments on the Interaction of Shock Waves With Boundary Layers on a Flat Plate
Authors: Barry F. W. , Shapiro A. H. , Neumann E. P.
Published: April 2021

Experimental results are presented in the form of schlieren and interferometer photographs showing the interaction of oblique shocks with laminar and turbulent boundary layers on a flat plate in a supersonic stream. The effects of variations in shock intensity and boundary-layer thickness were studied through a Mach number range of 2.0 to 2.5. A greater variety of shock boundary-layer interactions was discovered than had hitherto been suspected. The nature of the interaction was found not to be solely dependent upon whether the boundary layer is laminar or turbulent. A laminar layer proved to be more greatly affected by an incident oblique shock than a turbulent layer. With relatively intense shocks the boundary layer was influenced far upstream of the point of incidence. Injection of a high-speed air stream into a turbulent boundary layer altered significantly the manner of reflection of an incident shock.
On One-Term Approximations of Forced Nonharmonic Vibrations
Authors: Schwesinger G.
Published: April 2021

Steady forced vibrations of harmonically excited nonlinear systems deviate from a sinusoidal wave form, the magnitude of the deviation depending upon the frequency of the exciting force and the nature of the system concerned. Approximations by simple harmonic solutions suggested so far are either restricted to special vibration problems or generally fail to provide the desired accuracy without giving account of the errors committed. An improved general method is proposed and demonstrated, yielding the best accuracy attainable with harmonic solutions. This method, furthermore, gives the approximate root mean square of the error and thus allows for establishing dependable limits for its applicability.
Bending Vibrations of a Pipe Line Containing Flowing Fluid
Authors: Ashley Holt , Haviland George
Published: April 2021

Free vibrations and forced motions due to cross winds may both create important problems in the design of pipe lines supported above ground. An analytic investigation, based on simple beam theory, shows that the flow of fluid in such a pipe line produces marked damping tendencies and thus may reduce the severity of loading encountered. The time dependence of the fundamental mode of a simply supported pipe line is calculated for a number of mass-flow rates, the damping being observed to increase rapidly and the frequency to remain nearly constant over the practically important range. A method is outlined for studying forced vibration, higher modes, and other end conditions. Finally the problem is discussed in terms of traveling waves on an “infinite” unsupported pipe line.
Thermoelastic Stress Around a Cylindrical Inclusion of Elliptic Cross Section
Authors: Mindlin Raymond D. , Cooper Hilda L.
Published: April 2021

The two-dimensional equations of thermoelasticity are solved for the case of a uniform temperature change of an infinite medium containing a cylindrical inclusion of elliptic cross section. The problem is treated as one of plane strain in elliptic co-ordinates, and the solution is given in closed form. Formulas and curves are given for the maximum values of various components of stress at the interface between the inclusion and the surrounding medium.
Torsion of a Circular Shaft With a Number of Longitudinal Notches
Authors: Ōkubo H.
Published: April 2021

The object of this paper is to find a solution for the torsion problem of a circular shaft with a number of longitudinal semicircular notches. By using elementary functions the author has been able to simplify the numerical calculations in contrast to previous work in similar cases by other writers.
Plastic Biaxial Stress-Strain Relations for Alcoa 24S-T Subjected to Variable-Stress Ratios
Authors: Marin Joseph , Kotalik B. J.
Published: April 2021

Usually plastic biaxial stress-strain relations for metals have been determined for tests in which the ratios of the principal stresses have been maintained essentially constant. This paper presents biaxial plastic stress-strain relations for both constant and variable-stress ratios. The purpose of conducting the variable-stress-ratio tests is to attempt to prove whether the flow- or deformation-type theory is the correct theory for predicting plastic stress-strain relations. The paper also gives a comparison between the actual and theoretically predicted values of the biaxial yield, ultimate and fracture strengths, and the biaxial ductility. Various ratios of biaxial tensile stresses were investigated by subjecting tubular specimens to axial tension and internal pressure. The test results showed that the yield-strength values agree best with the distortion-energy theory. For the prediction of the plastic stress-strain relations the deformation-type theory was found to be in approximate agreement with the test results for both the constant- and variable-stress-ratio tests.
Elastic Torsion in the Presence of Initial Axial Stress
Authors: Goodier J. N.
Published: April 2021

The torsional rigidity, for small elastic torsion, of bars of thin-walled open section, is, in general, altered by initial tension, compression, bending, or other axial stress. This appears in the increase of torsional stiffness of strips due to tension, in the decrease to zero in open sections which buckle torsionally as columns, and also has an influence on lateral buckling of beams. This paper contains an extension of the Saint Venant solution for ordinary torsion to the problem of torsion in the presence of initial axial stress with any distribution on the cross section. The results are confirmed by tests, and validate the intuitively derived formulas which are in use.
The Uniform Distribution of a Fluid Flowing Through a Perforated Pipe
Authors: Dow Willard M.
Published: April 2021

A theoretical analysis is made of the flow through a perforated pipe with a closed end for the special case of a constant linear rate of discharge along the length of the pipe. The results of the fluid-flow considerations are applicable to many practical manifold systems. The practical significance of the results with respect to pipe burners for gaseous fuels is emphasized as the results make possible the design of simple high-capacity and extended-range pipe burners of industrial importance. The capacity of commercially available pipe burners may be increased several hundred per cent. The validity of the theoretical results was verified by experiment.
Measurements of Diffraction of Shock Waves and Resulting Loading of Structures
Authors: Bleakney Walker , White D. R. , Griffith W. C.
Published: April 2021

Although the idea of using a shock tube to generate waves of large amplitude and to study their properties is not new, nevertheless this technique has been improved greatly in recent years. This circumstance, taken together with good optical methods of measurement, has provided a powerful tool for the investigation of a great variety of problems in transient interactions of shocks and fluid flows with solid objects and with each other. This paper is concerned with the evolution in time of a flow pattern about an obstacle initially in still air, passed over by a sudden front of high-speed flow induced by a shock wave, the stream approaching a steady configuration. Such information is not only of interest in the theory of fluid dynamics but it also is of considerable practical importance, since the principal forces on the obstacle can be measured as a function of time, and the character of the loading determined. The main objective of this paper is to elucidate the method by giving examples of a great variety of experiments and at the same time to provide a large amount of basic data which may be used by others in various types of analyses.
The Use of Skewed Rolls in Calendering Operations
Authors: Carrier G. F.
Published: April 2021

In many commercial operations it is desirable to produce a uniform sheet of material by passing the viscous raw ingredients through rotating cylindrical rolls. With rolls supported at the ends only there is danger of wide variations in thickness of the finished product. This may be overcome by “skewing” the rolls the amount necessary for any given thickness and material properties. This paper presents an analytical approach to determining the optimum operating position of the rolls.
A Mathematical Representation of the Wheatley Heart Valve
Authors: McKee S. , Cuminato J. A. , Stewart I. W. , Wheatley D. J.
Published: April 2021

Starting from a hand-drawn contour plot, this note develops a set of intersecting and contiguous circles whose perimeter, upon extending appropriately to three dimensions, can be seen to be a natural mathematical representation of the Wheatley heart valve.
Ductile Damage Model Based on Void Growth Analysis for Application to Ductile Crack Growth Simulation
Authors: Yamada Takehisa , Ohata Mitsuru
Published: April 2021

This study aims to propose the damage model based on of the mechanism for ductile fracture related to void growth and to confirm the applicability of the proposed model to ductile crack growth simulation for steel. To figure out void growth behavior, elastoplastic finite element analyses using a unit cell model with an initial void were methodically performed. From the results of those analyses, it was evident that the relationships between normalized void volume fraction and normalized strain by each critical value corresponding to crack initiation were independent of stress–strain relationship of material and stress triaxiality state. Based on this characteristic associated with void growth, damage evolution law was derived. Then, using the damage evolution law, simple and phenomenological ductile damage model reflecting void growth behavior and ductility of material was proposed. To confirm the validation and application of the proposed damage model, the damage model was implemented in finite element models and ductile crack growth resistance was simulated for cracked components were performed. Then, the simulated results were compared with experimental ones and it was found that the proposed damage model could accurately predict ductile crack growth resistance and applied to ductile crack growth simulation.
Structural Integrity Assessment of Defected Gas Pipelines Using a Simplified Ductile Damage Model
Authors: Kim Ik-Joong , Kim Cheol-Man , Baek Jong-Hyun , Kim Young-Pyo , Lee Youngseog , Jang Yun-Chan
Published: April 2021

The finite element method using the damage model has been increasingly used to predict the failure of various structures. Thus, various damage models were presented, and recently, a phenomenological model called the local fracture strain model was presented, making it easy and accurate to predict the damage of the structure. This model has the advantage of defining fracture strain as a function of stress triaxiality with only a few notched tensile tests but has a limitation because it does not consider the damage evolution because of the void growth. This study presents an enhanced damage model that improves the accuracy of the failure simulation of defected structures by adding a parameter that considers stiffness degradation according to void growth to the damage model based on the fracture strain. Therefore, loading–unloading tests were conducted and the damage index of fracture was identified using a three-dimensional digital image correlation system. The failure simulation results using the proposed damage model were compared with experimental, such as notched tensile, single edge notched tension (SENT), and full-scale burst tests.
Functional response of Amblyseius andersoni and Neoseiulus neoreticuloides (Acari: Phytoseiidae) to adults of the wolfberry gall mite Aceria pallida (Acari: Eriophyoidae)

Authors: Fu Xiaotong , Liu Qingyan , Liu Junqing , Meng Ruixia
Published: April 2021

The gall mite, Aceria pallida Keifer (Acari: Eriophyoidae) is an economically important pest of wolfberry Lycium barbarum L. and can cause significant losses to plant production. Two species of phytoseiid predatory mites, Amblyseius andersoni Chant and Neoseiulus neoreticuloides Liang & Hu were found on L. barbarum in Bayan Nur city, Inner Mongolia, China. We assessed the potential of these two phytoseiid species as biological control agents against A. pallida, using functional response experiments with seven prey densities (5, 10, 20, 40, 60, 80 and 100 adults of A. pallida) on a wolfberry leaf under 25ºC ± 1ºC, 60% ± 5% RH and a 16:8 h (L:D) photoperiod. Overall, the predation of both species increased with increase in prey density. The consumption of A. andersoni female was significantly greater than that of conspecific males and N. neoreticuloides female at high prey densities. Both phytoseiid species displayed a type II functional response to A. pallida. Female A. andersoni had a higher attack rate (5.961) and a shorter handling time (0.014 d) than male A. andersoni (1.619; 0.019 d) and female N. neoreticuloides (0.719; 0.023 d). The maximum attack rate (T/Th) was estimated to be 71.43 and 52.63 for female and male A. andersoni, respectively, while it was 43.48 for female N. neoreticuloides. Both female and male A. andersoni consistently consumed significantly more prey than N. neoreticuloides across all densities of A. pallida adults.
Numerical study on lung ultrasound B-line formation as a function of imaging frequency and alveolar geometries
Authors: Peschiera Emanuele , Mento Federico , Demi Libertario
Published: April 2021

Lung ultrasound (LUS) has become a widely adopted diagnostic method for several lung diseases. However, the presence of air inside the lung does not allow the anatomical investigation of the organ. Therefore, LUS is mainly based on the interpretation of vertical imaging artifacts, called B-lines. These artifacts correlate with several pathologies, but their genesis is still partly unknown. Within this framework, this study focuses on the factors affecting the artifacts' formation by numerically simulating the ultrasound propagation within the lungs through the toolbox k-Wave. Since the main hypothesis behind the generation of B-lines relies on multiple scattering phenomena occurring once acoustic channels open at the lung surface, the impact of changing alveolar size and spacing is of interest. The tested domain is of size 4 cm × 1.6 cm, the investigated frequencies vary from 1 to 5 MHz, and the explored alveolar diameters and spacing range from 100 to 400 μm and from 20 to 395 μm, respectively. Results show the strong and entangled relation among the wavelength, the domain geometries, and the artifact visualization, allowing for better understanding of propagation in such a complex medium and opening several possibilities for future studies.
Analytical solution based on spatial distortion for a time-harmonic Green's function in a transverse isotropic viscoelastic solid
Authors: Royston Thomas J.
Published: April 2021

A strategy of spatial distortion to make an anisotropic problem become isotropic has been previously validated in two-dimensional transverse isotropic (TI) viscoelastic cases. Here, the approach is extended to the three-dimensional problem by considering the time-harmonic point force response (Green's function) in a TI viscoelastic material. The resulting wave field, exactly solvable using a Radon transform with numerical integration, is approximated via spatial distortion of the closed form analytical solution to the isotropic case. Different distortions are used, depending on whether the polarization of the wave motion is orthogonal to the axis of isotropy, with the approximation yielding differing levels of accuracy.
The Emotional Experiences of Paralympic Swimming Medalists: Not All Wins and Losses Are Equal
Authors: Martin Jeffrey
Published: April 2021

The goal of this study was to determine if emotional expressions at the end of swimmers’ 2016 Paralympic races varied according to medal won and if their race wins and losses were close or not close. Using FaceReader software, videos of 46 races of medal-winning Paralympic (Mage = 24.6;SD = 5.4) swimmers’ faces (78 males and 60 females) from 22 countries were analyzed. Silver medalists were angrier and sadder than gold medalists and angrier and more disgusted than bronze medalists. Swimmers who swam slower than their 2015 best time were angrier than Paralympians who swam faster. Paralympians who finished lower than their 2015 world ranking had more neutral emotions and were less happy than Paralympians who finished higher. Gold medalists who narrowly defeated silver medalists were less happy and more fearful than gold medalists who won easily. Bronze medalists with close wins had fewer neutral emotions and were happier, less angry, and more surprised than bronze medalists with not-close wins. All medalists with close wins were more surprised than medalists with easier wins. Bronze medalists with close losses to silver medalists were happier and less angry than bronze medalists who lost more easily. Effect sizes ranged fromd = 0.27 to 1.01. These results provide theoretical support to basic emotion theory and confirm the anecdotal observations that Paralympic competition generates wide-ranging and diverse emotions.
Dosage Individualization of Linezolid: Precision Dosing of Linezolid To Optimize Efficacy and Minimize Toxicity
Authors: Luque S. , Hope W. , Sorli L. , Muñoz-Bermudez R. , Campillo N. , Barceló-Vidal J. , Álvarez-Lerma F. , Horcajada J. P. , Masclans-Enviz J. R. , Neely M. , Grau S.
Published: April 2021

The high interindividual variability in the pharmacokinetics (PK) of linezolid has been described, which results in an unacceptably high proportion of patients with either suboptimal or potentially toxic concentrations following the administration of a fixed regimen. The aim of this study was to develop a population pharmacokinetic model of linezolid and use this to build and validate alogorithms for individualized dosing.
Phenotypic and Functional Characteristics of a Novel Influenza Virus Hemagglutinin-Specific Memory NK Cell
Authors: Zheng Jian , Wen Liyan , Yen Hui-Ling , Liu Ming , Liu Yinping , Teng Ooiean , Wu Wing-Fung , Ni Ke , Lam Kowk-Tai , Huang Chunyu , Yang Jiashuang , Lau Yu-Lung , Perlman Stanley , Peiris Malik , Tu Wenwei
Published: April 2021

In this study, we demonstrate a novel hemagglutinin (HA)-specific NKp46+NKG2A+NK cell subset induced by influenza A virus infection. These memory NK cells show virus-specific decreased cytotoxicity and increased gamma interferon (IFN-γ) on reencountering the same influenza virus antigen. In addition, they modulate host recall responses and CD8 T cell distribution, thus bridging the innate immune and adaptive immune responses during influenza virus infection.
Broadly Protective CD8+T Cell Immunity to Highly Conserved Epitopes Elicited by Heat Shock Protein gp96-Adjuvanted Influenza Monovalent Split Vaccine
Authors: Zhang Han , Zheng Huaguo , Guo Peng , Hu Liuyi , Wang Zihao , Wang Jiuru , Ju Ying , Meng Songdong
Published: April 2021

Owing to continuous mutations in hemagglutinin (HA) or neuraminidase (NA) or recombination of the gene segments between different strains, influenza viruses can escape the immune responses developed by vaccination. Thus, new strategies aimed to efficiently activate immune response that targets to conserved regions among different influenza viruses are urgently needed in designing broad-spectrum influenza vaccine.
Identification of Metabolically Quiescent
Leishmania mexicana
Parasites in Peripheral and Cured Dermal Granulomas Using Stable Isotope Tracing Imaging Mass Spectrometry
Authors: Kloehn Joachim , Boughton Berin A. , Saunders Eleanor C. , O’Callaghan Sean , Binger Katrina J. , McConville Malcolm J.
Published: April 2021

Many microbial pathogens switch between different growth and physiological states
in vivo
in order to adapt to local nutrient levels and host microbicidal responses. Heterogeneity in microbial growth and metabolism may also contribute to nongenetic mechanisms of drug resistance and drug failure.
Mitochondrial Pyruvate Carrier Subunits Are Essential for Pyruvate-Driven Respiration, Infectivity, and Intracellular Replication of Trypanosoma cruzi
Authors: Negreiros Raquel S. , Lander Noelia , Chiurillo Miguel A. , Vercesi Anibal E. , Docampo Roberto
Published: April 2021

Trypanosoma cruzi
is the causative agent of Chagas disease. Pyruvate is the end product of glycolysis, and its transport into the mitochondrion is mediated by the mitochondrial pyruvate carrier (MPC) subunits.
Aspirin Modulation of the Colorectal Cancer-Associated Microbe Fusobacterium nucleatum
Authors: Brennan Caitlin A. , Nakatsu Geicho , Gallini Comeau Carey Ann , Drew David A. , Glickman Jonathan N. , Schoen Robert E. , Chan Andrew T. , Garrett Wendy S.
Published: April 2021

There is an increasing understanding of the clinical correlations and potential mechanistic roles of specific members of the gut and tumoral microbiota in colorectal cancer (CRC) initiation, progression, and survival. However, we have yet to parlay this knowledge into better CRC outcomes through microbially informed diagnostic, preventive, or therapeutic approaches.
Thrombospondin-1 Restricts Interleukin-36γ-Mediated Neutrophilic Inflammation during Pseudomonas aeruginosa Pulmonary Infection
Authors: Peñaloza Hernán F. , Olonisakin Tolani F. , Bain William G. , Qu Yanyan , van der Geest Rick , Zupetic Jill , Hulver Mei , Xiong Zeyu , Newstead Michael W. , Zou Chunbin , Alder Jonathan K. , Ybe Joel A. , Standiford Theodore J. , Lee Janet S.
Published: April 2021

Pseudomonas aeruginosa
pulmonary infection can lead to exaggerated neutrophilic inflammation and tissue destruction, yet host factors that regulate the neutrophilic response is not fully known. IL-36γ is a proinflammatory cytokine that dramatically increases in bioactivity following N-terminal processing by proteases.
Multidisciplinary Approaches Identify Compounds that Bind to Human ACE2 or SARS-CoV-2 Spike Protein as Candidates to Block SARS-CoV-2–ACE2 Receptor Interactions
Authors: Day Christopher J. , Bailly Benjamin , Guillon Patrice , Dirr Larissa , Jen Freda E.-C. , Spillings Belinda L. , Mak Johnson , von Itzstein Mark , Haselhorst Thomas , Jennings Michael P.
Published: April 2021

SARS-CoV-2, the causative agent of COVID-19, has caused more than 60 million cases worldwide with almost 1.5 million deaths as of November 2020. Repurposing existing drugs is the most rapid path to clinical intervention for emerging diseases.
Shock-deformed zircon from the Chicxulub impact crater and implications for cratering process
Authors: Zhao Jiawei , Xiao Long , Xiao Zhiyong , Morgan Joanna V. , Osinski Gordon R. , Neal Clive R. , Gulick Sean P.S. , Riller Ulrich , Claeys Philippe , Zhao Shanrong , Prieur Nils C. , Nemchin Alexander , Yu Shuoran , IODP 364 Science Party
Published: April 2021

Large impact structures with peak rings are common landforms across the solar system, and their formation has implications for both the interior structure and thermal evolution of planetary bodies. Numerical modeling and structural studies have been used to simulate and ground truth peak-ring formative mechanisms, but the shock metamorphic record of minerals within these structures remains to be ascertained. We investigated impact-related microstructures and high-pressure phases in zircon from melt-bearing breccias, impact melt rock, and granitoid basement from the Chicxulub peak ring (Yucatán Peninsula, Mexico), sampled by the International Ocean Discovery Program (IODP)/International Continental Drilling Project (IODP-ICDP) Expedition 364 Hole M0077A. Zircon grains exhibit shock features such as reidite, zircon twins, and granular zircon including “former reidite in granular neoblastic” (FRIGN) zircon. These features record an initial high-pressure shock wave (>30 GPa), subsequent relaxation during the passage of the rarefaction wave, and a final heating and annealing stage. Our observed grain-scale deformation history agrees well with the stress fields predicted by the dynamic collapse model, as the central uplift collapsed downward-then-outward to form the peak ring. The occurrence of reidite in a large impact basin on Earth represents the first such discovery, preserved due to its separation from impact melt and rapid cooling by the resurging ocean. The coexistence of reidite and FRIGN zircon within the impact melt–bearing breccias indicates that cooling by seawater was heterogeneous. Our results provide valuable information on when different shock microstructures form and how they are modified according to their position in the impact structure, and this study further improves on the use of shock barometry as a diagnostic tool in understanding the cratering process.
Extensive decentralized hydrogen export from the Atlantis Massif
Authors: Lang Susan Q. , Lilley Marvin D. , Baumberger Tamara , Früh-Green Gretchen L. , Walker Sharon L. , Brazelton William J. , Kelley Deborah S. , Elend Mitchell , Butterfield David A. , Mau Aaron J.
Published: April 2021

Hydrogen is an important energy source for subsurface microbial communities, but its availability beyond the flow focused through hydrothermal chimneys is largely unknown. We report the widespread export of H2 across the Atlantis Massif oceanic core complex (30°N, Mid-Atlantic Ridge; up to 44 nM), which is distinct from the circulation system feeding the Lost City Hydrothermal Field (LCHF) on the massif's southern wall. Methane (CH4) abundances are generally low to undetectable (<3 nM) in fluids that are not derived from the LCHF. Reducing fluids exit the seafloor over a wide geographical area and depth range, including the summit of the massif and along steep areas of mass wasting east of the field. The depth of the fluids in the water column and their H2/CH4 ratios indicate that some are sourced separately from the LCHF. We argue that extensive H2 export is the natural consequence of fluid flow pathways strongly influenced by tectonic features and the volume and density changes that occur when ultramafic rocks react to form serpentinites, producing H2 as a by-product. Furthermore, the circulation of H2-rich fluids through uplifted mantle rocks at moderate temperatures provides geographically expansive and stable environmental conditions for the early evolution of biochemical pathways. These results provide insight into the spatial extent of H2- and CH4-bearing fluids associated with serpentinization, independent of the focused flow emanating from the LCHF.
Similar curvature-to-width ratios for channels and channel belts: Implications for paleo-hydraulics of fluvial ridges on Mars
Authors: Hayden Alistair T. , Lamb Michael P. , Carney Alexander J.
Published: April 2021

The surface of Mars contains abundant sinuous ridges that appear similar to river channels in planform, but they stand as topographic highs. Ridges have similar curvature-to-width ratios as terrestrial meandering rivers, which has been used to support the hypothesis that ridges are inverted channels that directly reflect channel geometry. Anomalously wide ridges, in turn, have been interpreted as evidence for larger rivers on Mars compared to Earth. However, an alternate hypothesis is that ridges are exhumed channel-belt deposits— a larger zone of relatively coarse-grained deposits formed from channel lateral migration and aggradation. Here, we measured landform wavelength, radius of curvature, and width to compare terrestrial channels, terrestrial channel belts, and martian ridges. We found that all three landforms follow similar scaling relations, in which ratios of radius of curvature to width range from 1.7 to 7.3, and wavelength-to-width ratios range from 5.8 to 13. We interpret this similarity to be a geometric consequence of a sinuous curved line of finite width. Combined with observations of ridge-stacking patterns, our results suggest that wide ridges on Mars could indicate fluvial channel belts that formed over significant time rather than anomalously large rivers.
Shutting down dust emission during the middle Holocene drought in the Sonoran Desert, Arizona, USA
Authors: Tau Guy , Crouvi Onn , Enzel Yehouda , Teutsch Nadya , Ginoux Paul , Rasmussen Craig
Published: April 2021

Long-term relationships between climate and dust emission remain unclear, with two prevailing but opposite hypotheses for effects of climate shifts: (1) increased dust emission due to increasing aridity imposing a vegetation change, or (2) decreased dust emission due to increasing aridity which imposes less stormy climate and reduced sediment supply. Here we test these hypotheses by analyzing an ~11-m-long core archiving Holocene dust trapped in Montezuma Well, a natural sinkhole in Arizona (southwestern United States), alongside current dust sources and transport pathways. Major elements indicate that Montezuma Well sediments originate from two end members: local carbonate bedrock and external siliceous dust. Core sediments are similar to the adjacent siliceous soils accumulated atop the bedrock, pointing to their eolian origin. Particle-size distributions reveal fine dust transported during winter from the northwestern Sonoran Desert and the Mojave Desert and coarse dust transported during summer from the southwestern Sonoran Desert, similar to current climate systems and dust pathways. A survey of potential dust sources indicates that current summer and winter dust sources in the Sonoran Desert are under a supply-limited state. Dust fluxes were higher during wetter phases of the Holocene when winter sources dominated. During the middle Holocene drought, dust fluxes were minimal and dominated by summer sources until dust input ceased as drought conditions did not produce enough floods to refill sources with sediments. We propose that in the Sonoran Desert, dust emission is strongly connected with climate, increasing during humid intervals and enhanced by fluvial sediment replenishment at dust sources.
Nitrogen Heterosubstitution in Graphene Nanoflakes: An Effective Approach to Improving Performance of Supercapacitors with Ionic Liquid Electrolyte
Authors: Arkhipova E. A. , Ivanov A. S. , Maslakov K. I. , Chernyak S. A. , Savilov S. V.
Published: April 2021

Nitrogen-doped graphene nanoflakes with a high nitrogen content (6.6 at %) and developed mesoporosity were synthesized via pyridine pyrolysis. They were tested in a supercapacitor with a non-aqueous electrolyte: a 1.2 M solution of ionic liquid Et4N+TFSI− in acetonitrile. It was found that incorporation of nitrogen into the graphene layers nearly tripled the specific capacitance of the electrode, compared to the undoped nanoflakes.
Comparison of identifiable and non-identifiable data linkage: health technology assessment of MitraClip using registry, administrative and mortality datasets
Authors: Keltie Kim , Cognigni Paola , Gross Sam , Urwin Samuel , Burn Julie , Cole Helen , Berry Lee , Patrick Hannah , Sims Andrew
Published: April 2021

Objectives

The UK MitraClip registry was commissioned by National Health Service (NHS) England to assess real-world outcomes from percutaneous mitral valve repair for mitral regurgitation using a new technology, MitraClip. This study aimed to determine longitudinal patient outcomes by linking to routine datasets: Hospital Episode Statistics (HES) Admitted Patient Care (APC) and Office of National Statistics.

Methods

Two methods of linkage were compared, using identifiable (NHS number, date of birth, postcode, gender) and non-identifiable data (hospital trust, age in years, admission, discharge and operation dates, operation and diagnosis codes). Outcome measures included: matching success, patient demographics, all-cause mortality and subsequent cardiac intervention.

Results

A total of 197 registry patients were eligible for matching with routine administrative data. Using identifiable linkage, a total of 187 patients (94.9%) were matched with the HES APC dataset. However, 21 matched individuals (11.2%) had inconsistencies across the datasets (eg, different gender) and were subsequently removed, leaving 166 (84.3%) for analysis. Using non-identifiable data linkage, a total of 170 patients (86.3%) were uniquely matched with the HES APC dataset.

Baseline patient characteristics were not significantly different between the two methods of data linkage. The total number of deaths (all causes) identified from identifiable and non-identifiable linkage methods was 37 and 40, respectively, and the difference in subsequent cardiac interventions identified between the two methods was negligible.

Conclusions

Patients from a bespoke clinical procedural registry were matched to routine administrative data using identifiable and non-identifiable methods with equivalent matching success rates, similar baseline characteristics and similar 2-year outcomes.
Digital health interventions for the management of mental health in people with chronic diseases: a rapid review
Authors: Sasseville Maxime , LeBlanc Annie , Boucher Mylène , Dugas Michèle , Mbemba Gisele , Tchuente Jack , Chouinard Maud-Christine , Beaulieu Marianne , Beaudet Nicolas , Skidmore Becky , Cholette Pascale , Aspiros Christine , Larouche Alain , Chabot Guylaine , Gagnon Marie-Pierre
Published: April 2021

Objective

Determine the effectiveness of digital mental health interventions for individuals with a concomitant chronic disease.

Design

We conducted a rapid review of systematic reviews. Two reviewers independently conducted study selection and risk of bias evaluation. A standardised extraction form was used. Data are reported narratively.

Interventions

We included systematic reviews of digital health interventions aiming to prevent, detect or manage mental health problems in individuals with a pre-existing chronic disease, including chronic mental health illnesses, published in 2010 or after.

Main outcome measure

Reports on mental health outcomes (eg, anxiety symptoms and depression symptoms).

Results

We included 35 reviews, totalling 702 primary studies with a total sample of 50 692 participants. We structured the results in four population clusters: (1) chronic diseases, (2) cancer, (3) mental health and (4) children and youth. For populations presenting a chronic disease or cancer, health provider directed digital interventions (eg, web-based consultation, internet cognitive–behavioural therapy) are effective and safe. Further analyses are required in order to provide stronger recommendations regarding relevance for specific population (such as children and youth). Web-based interventions and email were the modes of administration that had the most reports of improvement. Virtual reality, smartphone applications and patient portal had limited reports of improvement.

Conclusions

Digital technologies could be used to prevent and manage mental health problems in people living with chronic conditions, with consideration for the age group and type of technology used.
Can non-responders be ‘rescued’ by increasing exercise intensity? A quasi-experimental trial of individual responses among humans living with pre-diabetes or type 2 diabetes mellitus in Canada
Authors: Hrubeniuk Travis J , Bouchard Danielle R , Gurd Brendon J , Sénéchal Martin
Published: April 2021

Introduction

Exercise is recommended to improve glycaemic control. Yet, individual changes in glycaemic control following exercise can vary greatly, meaning while some significantly improve others, coined ‘non-responders’, do not. Increasing the intensity of exercise may ‘rescue’ non-responders and help generate a response to training. This trial will identify non-responders to changes in glycated haemoglobin (HbA1c) across inactive individuals living with pre-diabetes or type 2 diabetes mellitus following an aerobic exercise programme and evaluate if increasing training intensity will elicit beneficial changes to ‘rescue’ previously categorised non-responders.

Methods and analysis

This study will recruit 60 participants for a two-phase aerobic exercise training programme. Participants will be allocated to a control group or assigned to an intervention group. Control participants will maintain their current lifestyle habits. During phase 1, intervention participants will complete 16 weeks of aerobic exercise at an intensity of 4.5 metabolic equivalents (METs) for 150 min per week. Participants will then be categorised as responders or non-responders based on the change in HbA1c. For phase 2, participants will be blocked based on responder status and randomly allocated to a maintained intensity, or increased intensity group for 12 weeks. The maintained group will continue to train at 4.5 METs, while the increased intensity group will train at 6.0 METs for 150 min per week.

Ethics and dissemination

Results will be presented at scientific meetings and submitted to peer-reviewed journals. Publications and presentations related to the study will be authorised and reviewed by all investigators. Findings from this study will be used to provide support for future randomised control trials. All experimental procedures have been approved by the Research Ethics Board at the University of New Brunswick (REB: 2018–168).

Trial registration number

NCT03787836.
PAID study design on the role of PKC activation in immune/inflammation-related depression: a randomised placebo-controlled trial protocol
Authors: Guo Xiaoyun , Mao Ruizhi , Cui Lvchun , Wang Fan , Zhou Rubai , Wang Yun , Huang Jia , Zhu Yuncheng , Yao Yamin , Zhao Guoqing , Li Zezhi , Chen Jun , Wang Jinhui , Fang Yiru
Published: April 2021

Background

Inflammation that is mediated by microglia activation plays an important role in the pathogenesis of depression. Microglia activation can lead to an increase in the levels of proinflammatory cytokines, including TNF-α, which leads to neuronal apoptosis in the specific neural circuits of some brain regions, abnormal cognition and treatment-resistant depression (TRD). Protein kinase C (PKC) is a key regulator of the microglia activation process. We assume that the abnormality in PKC might result in abnormal microglia activation, neuronal apoptosis, significant changes in emotional and cognitive neural circuits, and TRD. In the current study, we plan to target at the PKC signal pathway to improve the TRD treatment outcome.

Methods and analysis

This is a 12-week, ongoing, randomised, placebo-controlled trial. Patients with TRD (N=180) were recruited from Shanghai Mental Health Center, Shanghai Jiao Tong University. Healthy control volunteers (N=60) were recruited by advertisement. Patients with TRD were randomly assigned to ‘escitalopram+golimumab (TNF-α inhibitor)’, ‘escitalopram+calcium tablet+vitamin D (PKC activator)’ or ‘escitalopram+placebo’ groups. We define the primary outcome as changes in the 17-item Hamilton Depression Rating Scale (HAMD-17). The secondary outcome is defined as changes in anti-inflammatory effects, cognitive function and quality of life.

Discussion

This study might be the first randomised, placebo-controlled trial to target at the PKC signal pathway in patients with TRD. Our study might help to propose individualised treatment strategies for depression.

Trial registration number

The trial protocol is registered with ClinicalTrials.gov under protocol ID 81930033 and ClinicalTrials.gov IDNCT04156425.
Multi-gene custom panels for the characterisation of metastatic colorectal carcinoma in clinical practice: express the role ofPIK3CAmutations
Authors: de Biase Dario , Malapelle Umberto , De Leo Antonio , Maloberti Thais , Visani Michela , Pisapia Pasquale , Acquaviva Giorgia , Pepe Francesco , Russo Gianluca , Iaccarino Antonino , Pession Annalisa , Tallini Giovanni , Troncone Giancarlo
Published: April 2021

Aims

In metastatic colorectal carcinomas (mCRC),RAS/RAFgenes mutations are first tested to determine the eligibility for anti-EGFR (Epidermal Growth Factor Receptor) therapy in combination with conventional cytotoxic agents. Recent advancements in next-generation sequencing (NGS) have highlighted the potential of multi-gene panels. This multi-gene analysis may provide useful information for the molecular characterisation of mCRC, other than the status ofRAS/RAFgenes. Aim of this study was to evaluate the feasibility of two NGS custom multi-gene panels in the characterisation of CRC cases and evaluating the relevance ofPIK3CAmutation in a routine cohort of consecutive CRC cases.

Methods

A total of 961 formalin-fixed and paraffin-embedded specimens from two medical centres (Bologna and Naples) were analysed using two lab-developed NGS multi-gene panels.

Results

KRASmutations (56.2%) were the more frequent alterations observed in our cohort. Intriguingly,PIK3CAmutations were more frequent (16.8%) than variants observed in the other two genes nowadays analysed in CRC clinical practice (NRASandBRAF, 4.2% and 9.6%, respectively). Moreover, in more than 10% of samples, coexistent mutations were detected in our cohort of CRC.

Conclusions

Our study demonstrates the feasibility and efficacy of lab-developed targeted multi-gene NGS panels in the clinical practice of CRC. Moreover, the data lead to hypothesise thatPIK3CAmutations, together with those ofRAS/BRAF, worth to be further investigated in clinical CRC specimens.
Oncolytic herpesvirus expressing PD-L1 BiTE for cancer therapy: exploiting tumor immune suppression as an opportunity for targeted immunotherapy
Authors: Khalique Hena , Baugh Richard , Dyer Arthur , Scott Eleanor M. , Frost Sally , Larkin Sarah , Lei-Rossmann Janet , Seymour Leonard W.
Published: April 2021

Background

Programmed death-ligand 1 (PD-L1) is an important immune checkpoint protein that can be regarded as a pan-cancer antigen expressed by multiple different cell types within the tumor. While antagonizing PD-L1 is well known to relieve PD-1/PD-L1-mediated T cell suppression, here we have combined this approach with an immunotherapy strategy to target T cell cytotoxicity directly toward PD-L1-expressing cells. We developed a bi-specific T cell engager (BiTE) crosslinking PD-L1 and CD3ε and demonstrated targeted cytotoxicity using a clinically relevant patient-derived ascites model. This approach represents an immunological ‘volte-face’ whereby a tumor immunological defense mechanism can be instantly transformed into an Achilles’ heel for targeted immunotherapy.

Methods

The PD-L1 targeting BiTE comprises an anti-PD-L1 single-chain variable fragment (scFv) or nanobody (NB) domain and an anti-CD3 scFv domain in a tandem repeat. The ability to activate T cell cytotoxicity toward PD-L1-expressing cells was established using human carcinoma cells and PD-L1-expressing human (‘M2’) macrophages in the presence of autologous T cells. Furthermore, we armed oncolytic herpes simplex virus-1 (oHSV-1) with PD-L1 BiTE and demonstrated successful delivery and targeted cytotoxicity in unpurified cultures of malignant ascites derived from different cancer patients.

Results

PD-L1 BiTE crosslinks PD-L1-positive cells and CD3ε on T cells in a ‘pseudo-synapse’ and triggers T cell activation and release of proinflammatory cytokines such as interferon-gamma (IFN-γ), interferon gamma-induced protein 10 (IP-10) and tumour necrosis factor-α (TNF-α). Activation of endogenous T cells within ascites samples led to significant lysis of tumor cells and M2-like macrophages (CD11b+CD64+ and CD206+/CD163+). The survival of CD3+ T cells (which can also express PD-L1) was unaffected. Intriguingly, ascites fluid that appeared particularly immunosuppressive led to higher expression of PD-L1 on tumor cells, resulting in improved BiTE-mediated T cell activation.

Conclusions

The study reveals that PD-L1 BiTE is an effective immunotherapeutic approach to kill PD-L1-positive tumor cells and macrophages while leaving T cells unharmed. This approach activates endogenous T cells within malignant ascites, generates a proinflammatory response and eliminates cells promoting tumor progression. Using an oncolytic virus for local expression of PD-L1 BiTE also prevents ‘on-target off-tumor’ systemic toxicities and harnesses immunosuppressive protumor conditions to augment immunotherapy in immunologically ‘cold’ clinical cancers.
Sense and sensitivity: can an inaccurate test be better than no test at all?
Authors: Pugh Jonathan , Wilkinson Dominic , Savulescu Julian
Published: April 2021

The UK government has put lateral flow antigen tests (LFATs) at the forefront of its strategy to scale-up testing in the coronavirus pandemic. However, evidence from a pilot trial using an LFAT to identify asymptomatic infections in the community suggested that the test missed over half of the positive cases in the tested population. This raises the question of whether it can be ethical to use an inaccurate test to guide public health measures. We begin by explicating different dimensions of test accuracy (sensitivity, specificity and predictive value), and why they matter morally, before highlighting key data from the Liverpool pilot. We argue that the poor sensitivity of the LFAT in this pilot trial suggests that there are important limitations to what we can expect these tests to achieve. A test with low sensitivity will provide false-negative results, and in doing so generate the risk of false assurance and its attendant moral costs. However, we also suggest that the deployment of an insensitive but specific test could identify many asymptomatic carriers of the virus who are currently being missed under existing arrangements. Having outlined ways in which the costs of false reassurance could potentially be mitigated, we conclude that the use of an insensitive LFAT in mass testing may be ethical if (1) it is used predominantly to identify positive cases, (2) it is a cost-effective method of achieving that goal and (3) if other public health tools can effectively prevent widespread false reassurance.