bluuebunny/crossref_metadata_2025 huggingface dataset:
A Flexible Multi-Modal Multi-User Traffic Simulation for Studying Complex Road Design
Authors: Miller Jack , Kalivarapu Vijay , Holm Michael , Finseth Tor , Williams Jordan , Winer Eliot
Published: November 2020

While there are many factors that affect traffic accidents, safe road design plays a key role. It is critical to understand traffic flow and driver response to various scenarios. Furthermore, with the inclusion of new traffic trends such as bicycle friendly roads and autonomous vehicles, it is ever more important to study the complex relationships between traffic entities. However, controlled experiments can be difficult to implement in the real world. Traffic simulation has been researched for decades to understand the flow of traffic in a variety of environments and how users interact within it. However, these platforms are limited in simulation and authoring capabilities, do not allow for multiple human agents, or are not accessible by roadway designers. This research explores the technical development of a multi-user multi-modal traffic simulation platform that expands on the capabilities of traditional traffic simulators. Traffic simulation of virtual cars and pedestrian agents were generated through VISSIM and networked into a simulation platform. Multiple human agents can interface with the system through a physical car and bicycle rig featuring both a virtual reality head mounted display and a multi-monitor display. Furthermore, the multi-user nature of the platform allows for a variety of complex research applications including multi-user behavior. By utilizing low-cost commodity hardware and software, the accessibility of this platform is greatly increased. A testbed environment was created to evaluate the technical limitations of the platform and assess where further work is needed. Through this evaluation, the authoring process and networking capabilities were optimized. Additionally, the core functionality of the platform, including the various simulator modes and multi-user functionality, was found to be successful. Through this research, combining commodity hardware with traffic simulation will allow a larger number of researchers to better understand traffic environments and how humans may interact within them.
Design Exploration of a Tensegrity-Based Twisting Wing
Authors: Kim Pham Nguyen , Peraza Hernandez Edwin A.
Published: November 2020

In the modern days of air travel, more fuel-efficient aircraft is desired to meet the demanding requirements of the long-haul market. This paper explores the feasibility of using a tensegrity column topology as the means for the internal mechanism of a twisting wing, which can be potentially applied to more fuel-efficient aircraft. This new morphing wing design removes the need for separate control surfaces such as ailerons and allow the wing to have a continuous surface which in turn will reduce aerodynamic drag and improve the overall performance. Furthermore, the tensegrity-based design can potentially reduce the weight of the wing by replacing conventional metal-based support structures with a lightweight tensegrity design. A design-of-experiments (DOE) study on the influence of the topological parameters of the torsional tensegrity mechanism on the achievable twist angle, structural mass, and the stresses in the different wing components is performed. It is found that for a wing with a span and chord length of 2 m, the maximum achievable twist angle from root to tip per unit mass, without any component exceeding their maximum allowable stress value, is 0.0659°/kg. The tensegrity column mechanism for this design consists of four torsional cells (equivalent to five ribs) and ten sets of actuating wires along the circumference of the column sections.
Global Product Design Platforming: A Comparison of Two Methods to Find Equilibrium Solutions
Authors: Case Sarah S. , Whitefoot Kate S.
Published: November 2020

We examine optimal-profit product design platforming problems for products sold across multiple markets. Firms have an incentive to platform to take advantage of cost reductions that are possible with increased production quantity, such as learning-by-doing. However, platforming may decrease sales compared to if the designs were customized for each market. The problem can be represented as a Nash equilibrium between multiple competing firms, each with a nonconvex mixed-integer nonlinear programing (MINLP) problem for maximizing their individual profits. We derive the Karush-Kuhn-Tucker (KKT) conditions for the problem and compare results from two algorithmic approaches: (1) an iterative MINLP approach that uses the BARON algorithm to solve each firm’s design and platforming problem and iterates until convergence to an equilibrium, and (2) an approach that solves the KKT conditions directly holding platforming decisions fixed, and compares profits for these platforming decisions to find an equilibrium. Results are presented for a case study of plug-in hybrid electric vehicles (PHEVs) where firms choose whether or not to platform the battery pack across the U.S. and China, and set the optimal battery capacity. We vary the learning rate and the difference in consumer willingness to pay for all-electric range between China and the U.S. Both algorithms agree on the same equilibrium solution in 98.4% of the cases. Results show that the optimum for each firm is to platform when learning rates are low, or the difference between optimal battery capacity in each market is relatively small.
The Determination of a Cost Optimal Design for a Multiple Stage Continuous Electrodialysis Desalination Device for Use in Domestic Point of Use Water Purification
Authors: Varner Hannah M. , Shah Sahil R. , Winter Amos G.
Published: November 2020

There is a large and growing demand for point of use (POU) water desalination in emerging economies, such as India, where there is a large reliance on brackish (saline) groundwater reservoirs to meet drinking needs. In this work we propose a design for a two-stage continuous ED system that addresses the requirements of the Indian market while providing a higher water recovery than existing POU reverse osmosis products. Optimization was applied to minimize capital cost while ensuring 90% recovery of the feed, 90% salt reduction, and 15 L/hr of desalinated water production. The optimized design had a capital cost of approximately US$ 106, which is below the retail price of current RO purifiers on the market. Therefore, two-stage continuous ED shows promise for being a cost-competitive but water-efficient alternative to POU RO in India.
StressGAN: A Generative Deep Learning Model for 2D Stress Distribution Prediction
Authors: Jiang Haoliang , Nie Zhenguo , Yeo Roselyn , Farimani Amir Barati , Kara Levent Burak
Published: November 2020

Using deep learning to analyze mechanical stress distributions has been gaining interest with the demand for fast stress analysis methods. Deep learning approaches have achieved excellent outcomes when utilized to speed up stress computation and learn the physics without prior knowledge of underlying equations. However, most studies restrict the variation of geometry or boundary conditions, making these methods difficult to be generalized to unseen configurations. We propose a conditional generative adversarial network (cGAN) model for predicting 2D von Mises stress distributions in solid structures. The cGAN learns to generate stress distributions conditioned by geometries, load, and boundary conditions through a two-player minimax game between two neural networks with no prior knowledge. By evaluating the generative network on two stress distribution datasets under multiple metrics, we demonstrate that our model can predict more accurate high-resolution stress distributions than a baseline convolutional neural network model, given various and complex cases of geometry, load and boundary conditions.
Broadening Participation: Over Ten Years of Outreach Within the IDETC-DED Community
Authors: de Vries Charlotte , Fu Kate , Starkey Elizabeth , Toh Christine , Damen Nicole B. , Joshi Shraddha , Sylcott Brian , Jacobson Kathryn
Published: November 2020

A core ethos of the engineering discipline is to tackle large, complex problems of central importance to society utilizing a range of technical knowledge and skills. One major barrier to this goal is the lack of diversity in the discipline, leading to a shortage of the talent pool, reduced capacity for innovation, and it can negatively impact the educational experience of engineering students. To respond to this charge, the Broadening Participation Committee (BPart) of the American Society of Mechanical Engineering’s Design Engineering Division (ASME DED) has conducted a number of activities aimed at fostering a diverse professional community and addressing the needs of people typically under-represented within engineering. This includes professional development workshops, networking sessions, travel funds available for graduate students and postdoctoral scholars, and micro-grants available for parents with young children.

This paper discusses the activities provided by the BPart Committee since 2013, as well as the outcomes and additional initiatives that occurred as a result of the BPart Activities. Examples of such activities include seven professional development workshops, three workshop panels, and seven networking receptions. In the workshop participant feedback, we see some effect when there is a female presenter over a male presenter, but this effect appears to be limited. A discussion on future activities of BPart is presented in order to continue to grow and foster this community.
Swarms of Aquatic Unmanned Surface Vehicles (USV), a Review From Simulation to Field Implementation
Authors: Ansary Jamal , O’Donnell Jacob , Fyza Nashiyat , Trease Brian
Published: November 2020

Swarm robotic is a field of multi-robotics in which the robot’s behavior is inspired from nature. With rapid development in the field of the multi-robotics and the lack of efficacy in traditional centralized controls method, decentralized nature inspired swarm algorithms were introduced to control the swarm behavior. Unmanned surface vehicles (USVs) are marine crafts that they can operate autonomously. Due to their potential in operating in different areas, these vehicles have been used for variety of reason including patrolling, border protection, environmental monitoring and oil spill confrontation. This paper provides a review of the Swarm of USVs, their application, simulation environments and the algorithms that has been used in the past and current projects.
Constraint-Based Analysis of Parallel Kinematic Articulated Wrist Mechanisms
Authors: Damerla Revanth , Awtar Shorya
Published: November 2020

This paper presents a systematic constraint-based analysis of the motion attributes of six parallel kinematic articulated wrist mechanisms from the existing literature. These motion attributes include the number, nature (i.e. pure rotation, or translation, or a combination), and location of mechanism’s Degrees of Freedom (DoFs) in the nominal and displaced configurations, range of operation along these DoFs, load transmission capability along these DoFs, and load bearing capability along the constraint directions. This systematic analysis reveals performance tradeoffs between these motion attributes for a given mechanism, as well as design tradeoffs across these multiple mechanisms with respect to these motion attributes. This analysis should help inform the suitability of a given mechanism for specific applications.
Design and Optimization of Functionally Graded Superelastic NiTi Stents
Authors: Khurana Jivtesh B. , Frecker Mary , Pauli Eric M.
Published: November 2020

Endoscopic stents are being used by surgeons in off-label uses to manage leaks and perforations in the gastrointestinal tract. Commercially available stents are primarily designed to open strictures in the esophagus through tissue compression. The stents incorporate a woven NiTi wire to produce a stiff and linear tubular shape that conforms to the esophagus. In off-label uses, where the stents are placed in non-esophageal locations the stents must bend, the stents show a high propensity to migrate from their initial location causing unwanted complications. In this paper, a new stent design incorporating functionally graded NiTi is presented and explored. First, a functionally graded NiTi stent design is proposed. Next, a mechanical model using finite element analysis is developed to predict the bending moment and stiffness of the functionally graded stent designs. Finally, the mechanical model is coupled with a genetic algorithm in MATLAB to identify optimal designs. For a 90° bending angle, the best design parameters of the newly proposed flexible stents are found for three different stent design families. The results of the functionally graded stents show how tailoring the material properties locally in a structure can lead to highly compliant behavior. The tailoring of the geometric and material design developed may be applied to design of highly flexible and optimized medical devices.
Generative Infills for Additive Manufacturing Using Space-Filling Polygonal Tiles
Authors: Ebert Matthew , Subramanian Sai Ganesh , Akleman Ergun , Krishnamurthy Vinayak R.
Published: November 2020

We study a new class of infill patterns, that we call wallpaper-infills for additive manufacturing based on space-filling shapes. To this end, we present a simple yet powerful geometric modeling framework that combines the idea of Voronoi decomposition space with wallpaper symmetries defined in 2-space. We first provide a geometric algorithm to generate wallpaper-infills and design four special cases based on selective spatial arrangement of seed points on the plane. Second, we provide a relationship between the infill percentage to the spatial resolution of the seed points for our cases thus allowing for a systematic way to generate infills at the desired volumetric infill percentages. Finally, we conduct a detailed experimental evaluation of the of these four cases to study their mechanical behavior under tensile loading.
Stability Region-Based Analysis of Walking and Push Recovery Control
Authors: Peng William Z. , Song Hyunjong , Kim Joo H.
Published: November 2020

Push recovery is a vital aspect of balance stability control in biped robots. In this work, the response of a biped system to unexpected external perturbations is analyzed for different tasks and controllers using stability criteria based on balanced and steppable regions. The steppable region for a given step length and the balanced regions for single and double support contacts are constructed for a biped robot using optimization with its system dynamics, kinematic limits, actuation limits, and contact interactions with the environment. The regions are compared with those of a human subject to demonstrate that human gait exhibits unbalanced (but steppable) phases largely absent in robotic gait. These regions are also applied to a comparative analysis against capturability, where the computed steppable region is significantly larger than the capture region of an equivalent reduced-order model. The stability regions are also used to compare the performance of controllers during a double support balancing task. The implemented hip, knee, and ankle strategy-based controller led to improved stabilization — i.e., decreased foot tipping and time required to balance — relative to an existing hip and ankle controller and a gyro feedback controller. The proposed approaches are applicable to the analysis of any bipedal task and stability controller in general.
Design of an Onboard Directional Anemometer for Bicycles
Authors: Hurtado Valentina , Arango Santiago , Muñoz Luis , López Omar
Published: November 2020

Wind speed has large influence on the results of road tests applied to bicycles. For this reason, this paper presents the design process of an onboard anemometer dedicated to bicycle testing. The design provides an affordable way to quantify both magnitude and direction of the wind velocity relative to the bicycle, allowing recording on arbitrary wind conditions that could arise during a test.

The design methodology was structured with two major phases. The first was centered on the proof-of-concept for the use of a multi-hole pitot tube as main component for the onboard anemometer. The second was focused on the design of the structure, considering both packaging and structural integrity.

The prototype of anemometer was tested in a wind tunnel to verify its performance, and it was also tested under severe vibrations to verify its structural integrity. The results showed that this concept can be used as a part of the bicycle instrumentation for road tests.
Paired Computer-Aided Design: The Effect of Collaboration Mode on Differences in Model Quality
Authors: Arshad Hamza , Phadnis Vrushank , Olechowski Alison
Published: November 2020

We present the results of an experiment investigating two different modes of collaboration on a series of computer-aided design (CAD) tasks. Inspired by the pair programming literature, we anticipate that partners working in a fully synchronous collaborative CAD environment will achieve different levels of quality in CAD models depending on their mode of collaboration — one in which the pair is free to work in parallel, and another where the pair must coordinate to share one control.

We found that a shared CAD control led to significantly better overall CAD quality than parallel CAD control. In addition, the shared control mode led to more complete and consistent CAD models, as well as the tendency for participants to follow instructions to correctly replicate features for the design task. As is predicted in the literature, a trade-off relationship (albeit weak) between quality and speed via the parallel collaboration was found. In contrast, the shared control mode shows no clear relationship between speed and quality.

Collaborative CAD is increasingly seen as an appealing tool for modern product design teams. This study suggests that the benefits of this tool are not solely the effect of the tool itself, but result from the collaboration style of the designers using the tool.
Extracting Maximum Power in the Presence of Internal Inductance of Electromagnetic Energy Harvesting Systems
Authors: Sharma Yamini , Zuo Lei
Published: November 2020

In this paper, the effect of internal inductance of electromagnetic generators in the field of energy harvesting is discussed. Electromagnetic energy harvesters are typically operated at low frequencies. This results in the generator internal inductor impedance being significantly less than the generator internal resistance. However, at high frequencies, this inductance can no longer be ignored. Therefore, to maximize the harvested power, the internal inductance must be considered while designing the power electronics. This paper presents two methods to tackle this issue. The first method involves making use of a discrete capacitor which is able to reduce the inductance effect not just at resonant frequency but for the entire operating frequency range. The second method makes use of a concept similar to synchronized switching harvesting on inductors (SSHI) in piezoelectric energy harvesting. A capacitor and switch are added in the electromagnetic energy harvesting circuit to reduce the generator internal inductance effect. This method not only provides the benefit of performing well in the entire operating frequency range but also eliminates the need for precise maximum power tracking techniques, which further helps in reducing the circuit losses. Simulation results show a maximum power output increase of 56%.
Influence of the Chainring Geometry on the Critical Power of Recreational Cyclists
Authors: Acevedo Orlando , Muñoz Luis , Polanco Alejandra , Suárez Daniel
Published: November 2020

Science has come to a disagreement regarding the real effect that chainrings’ geometry has on cyclists’ performance. In this study, the influence of the use of a noncircular chainring on recreational cyclists’ performance is determined through experimental power delivery tests. A critical power model was used to estimate variations on cyclists’ performance. In addition, a new protocol for estimating critical power was proposed.

Fourteen recreational cyclists (two females and twelve males) performed a series of self-paced constant-time tests with a circular and a noncircular (i.e., Osymetric) chainring during two different test sessions. Power output, cadence and time were registered to compute the critical power.

According to the results of this study, it seems there is a change in the critical power of the majority of the recreational cyclists due to the use of a noncircular chainring. Thus, a performance improvement was obtained during long-endurance tests. However, the order of the tests (i.e., starting with the circular chainring or starting with the noncircular chainring) was proven to have an impact on the results due to a familiarization effect to the test conditions. Finally, a new protocol to estimate the critical power of a cyclist by performing a single riding session was proposed and assessed on a pilot test (i.e., error < 3%).
Finite Element Model for Prediction of Ground Vehicle Mobility Over Vegetation Covered Terrains
Authors: Wasfy Tamer , Wasfy Hatem , Jayakumar Paramsothy , Sanikommu Srinivas
Published: November 2020

A finite element vegetation model is presented for predicting the dynamic interaction of ground vehicles with vegetation. The purpose of the model is to predict ground vehicle mobility over vegetation covered terrains. The types of vegetation can range from small diameter highly compliant stems to large stiff trees. Those include various types of vegetation such as grass, crops, shrubs/bushes, small trees, and large trees. Mobility measures which can be predicted include maximum safe vehicle speed along a specified path, tire slip, and fuel consumption. The ground vehicles are modeled using high-fidelity multibody dynamics models. The vegetation stems are modeled using an arrangement of thin and/or thick beam finite elements. The thin beam model uses the torsional spring beam formulation for small flexible vegetation and only includes the axial and bending beam responses. The thick beam model includes axial, bending, torsional, and shear beam responses and uses a lumped parameter beam element which connects two rigid body type nodes. The vegetation model includes the effects of normal contact and friction with the vehicle and between stems, stem breaking, and stem aerodynamic forces.
Stakeholder Perceptions of Requirements Elicitation Interviews With and Without Prototypes in a Cross-Cultural Design Setting
Authors: Coulentianos Marianna J. , Daly Shanna R. , Sienko Kathleen H.
Published: November 2020

Using prototypes during design requirements elicitation (RE) interviews with stakeholders can encourage stakeholder participation. Stakeholder engagement and the quality of the feedback provided can be influenced by the format of the RE interview, especially in a cross-cultural design setting. Although the selection of design practices is typically motivated by designer preferences and design outcomes, deliberate consideration of stakeholder preferences and perceptions may lead to a more nuanced understanding of when and how to best leverage particular design practices. This study investigated the influence of the number of prototypes (here, assistive devices for removing subdermal contraceptive implants) presented during RE interviews on Ghanaian stakeholder preferences. The findings revealed that most participants (n = 34, 94%) preferred the presence of one or more prototypes compared to no prototypes during the interviews because prototypes enabled participants to better understand the design space, provide accurate feedback, and evaluate ideas. Prototypes provided participants with a basis for answering designers’ questions. When they were not provided with a prototype, participants explained that they imagined a novel device concept or recalled a device from prior experiences. Further, participants preferred the use of three prototypes versus a single prototype because multiple prototypes enabled them to compare across designs and make choices. These findings suggest that designers seeking requirements-related input from stakeholders at the problem definition stage should consider using one or more prototypes, unless they are interested in collecting design ideas from stakeholders.
Analysis of the Relative Motion Between the Socket and Residual Limb in Transtibial Amputees While Wearing a Transverse Rotation Adapter
Authors: Pew Corey A. , Roelker Sarah A. , Klute Glenn K. , Neptune Richard R.
Published: November 2020

The coupling between the residual limb and the lower-limb prosthesis is not rigid. As a result, external loading produces movement between the prosthesis and residual limb that can lead to undesirable soft-tissue shear stresses. As these stresses are difficult to measure, limb loading is commonly used as a surrogate. However, the relationship between limb loading and the displacements responsible for those stresses remains unknown. To better understand the limb motion within the socket, an inverse kinematic analysis was performed to estimate the motion between the socket and tibia for 10 individuals with a transtibial amputation performing walking and turning activities at 3 different speeds. The authors estimated the rotational stiffness of the limb-socket body to quantify the limb properties when coupled with the socket and highlight how this approach could help inform prosthetic prescriptions. Results showed that peak transverse displacement had a significant, linear relationship with peak transverse loading. Stiffness of the limb-socket body varied significantly between individuals, activities (walking and turning), and speeds. These results suggest that transverse limb loading can serve as a surrogate for residual-limb shear stress and that the setup of a prosthesis could be individually tailored using standard motion capture and inverse kinematic analyses.
Early Physical Activity Adoption Predicts Longer-Term Physical Activity Among Individuals Inactive at Baseline
Authors: Unick Jessica L. , Walkup Michael P. , Miller Michael E. , Apolzan John W. , Brubaker Peter H. , Coday Mace , Hill James O. , Jakicic John M. , Middelbeek Roeland J.W. , West Delia , Wing Rena R. , _ _
Published: November 2020

Background: To examine the relationship between early physical activity (PA) adoption (2, 3, and 4 mo) and longer-term PA adherence (1 y) among individuals who were inactive at baseline and received a lifestyle intervention. Methods: Participants (n = 637) received weekly behavioral weight loss sessions, calorie reduction, and PA goals (50–175 min/wk progression). PA was assessed via self-reported measures at baseline, months 2 to 4, and 1 year. Results: PA at months 2 to 4 was significantly correlated with PA at 1 year (rs = .29–.35, P < .01). At all early time points, those failing to meet the prescribed PA goal (early nonadopters) engaged in significantly less PA at 1 year than those meeting the early PA goal (initial adopters). For example, using 2-month criteria, initial adopters engaged in 108.3 minutes per week more at 1 year compared with early nonadopters (P < .01) and had 2.8 times the odds (95% confidence interval, 1.9–4.2) of meeting the 1-year PA goal (≥175 min/wk, P < .01). Conclusions: Failure to achieve PA goals at 2, 3, or 4 months results in less overall PA at 1 year. Thus, PA observed as early as month 2 may be a useful indicator for identifying at-risk individuals who may benefit from more intensive PA intervention strategies.
Studies of Physical Activity and COVID-19 During the Pandemic: A Scoping Review
Authors: Caputo Eduardo L. , Reichert Felipe F.
Published: November 2020

Background: This scoping review aimed to identify the available evidence related to physical activity (PA) and the coronavirus disease (COVID-19) pandemic. Methods: A search in 6 databases (PubMed, Embase, SPORTDiscus, Scopus, Web of Science, and CINAHL) was conducted on July 23, 2020. Medical subject headings and keywords related to PA and COVID-19 were combined to conduct the online search, which covered the period from January to July 2020. Results: Overall, 1784 articles were retrieved. After duplicate removal and title, abstract, and full-text screening, 41 articles were included. Most of the included studies were quantitative and collected data through online interviews/questionnaires, with sample sizes larger than 100 and composed by adults and older adults. Changes in PA levels due to the COVID-19 pandemic were the most assessed outcome, followed by the association between mental health issues and PA. Only 2 studies assessed the direct effects of PA on COVID-19. Conclusion: Most of the evidence identified a decrease in PA levels due to social distancing measures and that PA might help to decrease the mental health burden related to the COVID-19 outbreak.
The GATOR–Rag GTPase pathway inhibits mTORC1 activation by lysosome-derived amino acids
Authors: Hesketh Geoffrey G. , Papazotos Fotini , Pawling Judy , Rajendran Dushyandi , Knight James D. R. , Martinez Sebastien , Taipale Mikko , Schramek Daniel , Dennis James W. , Gingras Anne-Claude
Published: November 2020

Intricacies of amino acid sensing

The way in which cells sense amino acids derived from external proteins taken up by micropinocytosis and then degraded in the lysosome turns out to be different from the way in which they sense external amino acids taken up through transporters in the plasma membrane. Both sources of amino acids end up activating the mechanistic target of rapamycin complex 1 (mTORC1) protein kinase complex. However, Hesketh
et al.
found that cultured human cells sense amino acids derived from exogenous proteins in late endosomes by a mechanism independent of the Rag guanosine triphosphatases (GTPases) that control mTORC1 activation in response to external amino acids. Furthermore, the GATOR GTPase had an inhibitory effect on mTORC1 activation in response to proteins processed through the lysosome, opposite to its role in sensing amino acids taken up across the plasma membrane.

Science
, this issue p.
351
Species richness and redundancy promote persistence of exploited mutualisms in yeast
Authors: Vidal Mayra C. , Wang Sheng Pei , Rivers David M. , Althoff David M. , Segraves Kari A.
Published: November 2020

Species richness maintains mutualisms

Mutualistic communities of species that benefit each other are ubiquitous in ecosystems and are important for ecosystem functioning. However, the relationship between the persistence of mutualisms and species richness has remained unclear. Vidal
et al.
used a synthetic mutualism in brewer's yeast to experimentally test whether species richness buffers mutualistic communities against exploitation by species that do not provide benefits in return. They showed that richer mutualist communities survive exploitation more often than pairwise mutualisms and that higher species richness and functional redundancy allow mutualist communities to persist in the presence of exploiters. These results provide experimental support for the hypothesis that species richness is necessary for the function and maintenance of mutualistic communities.

Science
, this issue p.
346
Engineering synthetic morphogen systems that can program multicellular patterning
Authors: Toda Satoshi , McKeithan Wesley L. , Hakkinen Teemu J. , Lopez Pilar , Klein Ophir D. , Lim Wendell A.
Published: November 2020

Engineering synthetic morphogens

Morphogens provide positional information during tissue development. For this behavior to occur, morphogens must spread out and form a concentration gradient; however, their mechanism of transport remains a matter of debate. Stapornwongkul
et al.
now show that in the presence of extracellular binding elements (binders), the inert green fluorescent protein (GFP) can form a detectable concentration gradient by diffusion in the developing fly wing (see the Perspective by Barkai and Shilo). When combining the expression of nonsignaling binders and receptors engineered to respond to GFP, a synthetic GFP gradient can substitute for a natural morphogen to organize growth and patterning. In related work, Toda
et al.
also show that GFP can be converted into a morphogen by providing anchoring interactions that tether the molecule, forming a gradient that can be recognized by synthetic receptors that activate gene expression. These synthetic morphogens can be used to program de novo multidomain tissue patterns. These results highlight core mechanisms of morphogen signaling and patterning and provide ways to program spatial tissue organization independently from endogenous morphogen pathways.

Science
, this issue p.
321
, p.
327
; see also p.
292
Lubricating lipids in hydrogels
Authors: Schmidt Tannin A.
Published: November 2020

A self-renewing lipid layer substantially reduces friction and wear of a hydrogel surface
Experiments in creativity
Making Art Work
W. Patrick McCray
MIT Press, 2020. 384 pp.
Authors: Ockert Ingrid
Published: November 2020

Artists and engineers joined forces in the 1960s, blurring the line between art and technology
Joe L. Martinez Jr. (1944–2020)
Authors: Trujillo Keith A. , Quiñones-Hinojosa Alfredo , Thompson Kenira J.
Published: November 2020

Neuroscientist and advocate of inclusion
The Antifungal and Synergistic Effect of Bisphosphonates in
Cryptococcus
Authors: Kane Aidan , Campbell Leona , Ky Diana , Hibbs David , Carter Dee
Published: November 2020

New treatment strategies are required for cryptococcosis, a leading mycosis in HIV-AIDS patients. Following the identification of
Cryptococcus
proteins differentially expressed in response to fluconazole, we targeted farnesyl pryrophosphate synthetase (FPPS), an enzyme in the squalene biosynthesis pathway, using nitrogenous bisphosphonates. We hypothesized that these would disrupt squalene synthesis and thereby produce synergy with fluconazole, which acts on a downstream pathway that requires squalene.
Cardiotropic Isolates of Listeria monocytogenes with Enhanced Vertical Transmission Dependent upon the Bacterial Surface Protein InlB
Authors: Lamond Nicole M. , McMullen P. David , Paramasvaran Dhanendra , Visvahabrathy Lavanya , Eallonardo Samuel J. , Maheswhari Akhil , Freitag Nancy E.
Published: November 2020

Listeria monocytogenes
is a facultative Gram-positive intracellular bacterium that is capable of causing serious invasive infections in pregnant women, resulting in abortion, still-birth, and disseminated fetal infection. Previously, a clinical
L. monocytogenes
isolate, 07PF0776, was identified as having an enhanced ability to target cardiac tissue. This tissue tropism appeared to correlate with amino acid variations found within internalin B (InlB), a bacterial surface protein associated with host cell invasion.
The Role of
luxS
in Histophilus somni Virulence and Biofilm Formation
Authors: Pan Yu , Siddaramappa Shivakumara , Sandal Indra , Dickerman Allan , Bandara Aloka B. , Inzana Thomas J.
Published: November 2020

S
-Ribosylhomocysteinase (LuxS) is required for the synthesis of the autoinducer-2 (AI-2) quorum-sensing signaling molecule in many Gram-negative bacteria. The bovine (and ovine) opportunistic pathogen
Histophilus somni
contains
luxS
and forms a biofilm containing an exopolysaccharide (EPS) in the matrix. Since biofilm formation is regulated by quorum sensing in many bacteria, the roles of
luxS
in
H. somni
virulence and biofilm formation were investigated.
Changes in SARS-CoV-2 Spike versus Nucleoprotein Antibody Responses Impact the Estimates of Infections in Population-Based Seroprevalence Studies
Authors: Fenwick Craig , Croxatto Antony , Coste Alix T. , Pojer Florence , André Cyril , Pellaton Céline , Farina Alex , Campos Jérémy , Hacker David , Lau Kelvin , Bosch Berend-Jan , Gonseth Nussle Semira , Bochud Murielle , D’Acremont Valerie , Trono Didier , Greub Gilbert , Pantaleo Giuseppe
Published: November 2020

In the present study, we have determined SARS-CoV-2-specific antibody responses in sera of acute and postinfection phase subjects. Our results indicate that antibody responses against viral S and N proteins were equally sensitive in the acute phase of infection, but that responses against N appear to wane in the postinfection phase where those against the S protein persist over time. The most sensitive serological assay in both acute and postinfection phases used the native S protein trimer as the binding antigen, which has significantly greater conformational epitopes for antibody binding compared to the S1 monomer protein used in other assays. We believe these results are extremely important in order to generate correct estimates of SARS-CoV-2 infections in the general population. Furthermore, the assessment of antibody responses against the trimeric S protein will be critical to evaluate the durability of the antibody response and for the characterization of a vaccine-induced antibody response.
Conjugal DNA Transfer in Sodalis glossinidius, a Maternally Inherited Symbiont of Tsetse Flies
Authors: Kendra Christopher G. , Keller Chelsea M. , Bruna Roberto E. , Pontes Mauricio H.
Published: November 2020

Tsetse flies are the insect vectors of
T. brucei
, the causative agent of African sleeping sickness—a zoonotic disease that inflicts a substantial economic cost on a broad region of sub-Saharan Africa. Notably, tsetse flies can be infected with the bacterium
S. glossinidius
to establish an asymptomatic chronic infection. This infection can be inherited by future generations of tsetse flies, allowing
S. glossinidius
to spread and persist within populations. To this effect,
S. glossinidius
has been considered a potential expression platform to create flies which reduce
T. brucei
stasis and lower overall parasite transmission to humans and animals. However, the efficient genetic manipulation of
S. glossinidius
has remained a technical challenge due to its complex growth requirements and uncharacterized physiology. Here, we exploit a natural mechanism of DNA transfer among bacteria and develop an efficient technique to genetically manipulate
S. glossinidius
for future studies in reducing trypanosome transmission.
i-CONTENT tool for assessing therapeutic quality of exercise programs employed in randomised clinical trials
Authors: Hoogeboom Thomas J , Kousemaker Martijn C , van Meeteren Nico LU , Howe Tracey , Bo Kari , Tugwell Peter , Ferreira Manuela , de Bie Rob A , van den Ende Cornelia HM , Stevens-Lapsley Jennifer E
Published: November 2020

Objective

When appraising the quality of randomised clinical trial (RCTs) on the merits of exercise therapy, we typically limit our assessment to the quality of the methods. However, heterogeneity across studies can also be caused by differences in the quality of the exercise interventions (ie, ‘the potential effectiveness of a specific intervention given the potential target group of patients’)—a challenging concept to assess. We propose an internationally developed, consensus-based tool that aims to assess the quality of exercise therapy programmes studied in RCTs: the international Consensus on Therapeutic Exercise aNd Training (i-CONTENT) tool.

Methods

Forty-nine experts (from 12 different countries) in the field of physical and exercise therapy participated in a four-stage Delphi approach to develop the i-CONTENT tool: (1) item generation (Delphi round 1), (2) item selection (Delphi rounds 2 and 3), (3) item specification (focus group discussion) and (4) tool development and refinement (working group discussion and piloting).

Results

Out of the 61 items generated in the first Delphi round, consensus was reached on 17 items, resulting in seven final items that form the i-CONTENT tool: (1) patient selection; (2) qualified supervisor; (3) type and timing of outcome assessment; (4) dosage parameters (frequency, intensity, time); (5) type of exercise; (6) safety of the exercise programme and (7) adherence to the exercise programme.

Conclusion

The i-CONTENT-tool is a step towards transparent assessment of the quality of exercise therapy programmes studied in RCTs, and ultimately, towards the development of future, higher quality, exercise interventions.
Sleep and the athlete: narrative review and 2021 expert consensus recommendations
Authors: Walsh Neil P , Halson Shona L , Sargent Charli , Roach Gregory D , Nédélec Mathieu , Gupta Luke , Leeder Jonathan , Fullagar Hugh H , Coutts Aaron J , Edwards Ben J , Pullinger Samuel A , Robertson Colin M , Burniston Jatin G , Lastella Michele , Le Meur Yann , Hausswirth Christophe , Bender Amy M , Grandner Michael A , Samuels Charles H
Published: November 2020

Elite athletes are particularly susceptible to sleep inadequacies, characterised by habitual short sleep (<7 hours/night) and poor sleep quality (eg, sleep fragmentation). Athletic performance is reduced by a night or more without sleep, but the influence on performance of partial sleep restriction over 1–3 nights, a more real-world scenario, remains unclear. Studies investigating sleep in athletes often suffer from inadequate experimental control, a lack of females and questions concerning the validity of the chosen sleep assessment tools. Research only scratches the surface on how sleep influences athlete health. Studies in the wider population show that habitually sleeping <7 hours/night increases susceptibility to respiratory infection. Fortunately, much is known about the salient risk factors for sleep inadequacy in athletes, enabling targeted interventions. For example, athlete sleep is influenced by sport-specific factors (relating to training, travel and competition) and non-sport factors (eg, female gender, stress and anxiety). This expert consensus culminates with a sleep toolbox for practitioners (eg, covering sleep education and screening) to mitigate these risk factors and optimise athlete sleep. A one-size-fits-all approach to athlete sleep recommendations (eg, 7–9 hours/night) is unlikely ideal for health and performance. We recommend an individualised approach that should consider the athlete’s perceived sleep needs. Research is needed into the benefits of napping and sleep extension (eg, banking sleep).
How sensitive are avoidable emergency department attendances to primary care quality? Retrospective observational study
Authors: Parkinson Beth , Meacock Rachel , Checkland Kath , Sutton Matt
Published: November 2020

Background

Improvements in primary care quality are often proposed as a solution to rises in emergency department (ED) attendances. However, there is little agreement on what constitutes an avoidable attendance, and the relationship between primary care quality and ED demand remains poorly understood.

Objective

To estimate the size of the associations between primary care quality and volumes of ED attendances classified as avoidable.

Methods

Retrospective observational study of all attendances at EDs in England during 2015/2016, applying three definitions of avoidable attendance. We linked practice-level counts of attendances to seven measures of primary care access, patient experience and clinical quality for 7521 practices. We used count data regressions to associate attendance counts with levels of quality. We then calculated proportions of attendances associated with levels of primary care quality below the national average.

Results

Attendance volumes were negatively related to three of the seven quality measures. Incidence rate ratios (IRRs) for all attendances associated with 10 percentage-point differences in quality were 0.987 for clinical quality and 0.987 for easy telephone access and 0.978 for ability to get an appointment. These associations were relatively stronger for narrower definitions of avoidable attendances (for the narrowest definition, IRRs=0.966, 0.976 and 0.934, respectively) but represented fewer attendances in absolute terms. 341 000 (2.4%) attendances were associated with levels of primary care quality below the national average in 2015/2016.

Conclusion

ED attendances are sensitive to primary care quality, but magnitudes of these associations are small. Attendances are much less responsive to differences in primary care quality than indicated by estimates of the prevalence of avoidable attendances. This may explain the failure of initiatives to reduce attendances through primary care improvements.
Mutational profiling in suspected triple-negative essential thrombocythaemia using targeted next-generation sequencing in a real-world cohort
Authors: Michail Olga , McCallion Patrick , McGimpsey Julie , Hindley Andrew , Greenfield Graeme , McAllister Roisin , Feerick John , Arnold Claire , Cross Nick , Cuthbert Robert , McMullin Mary F , Catherwood Mark A
Published: November 2020

Essential thrombocythaemia (ET) is driven by somatic mutations involving theJAK2,CALRandMPLgenes. Approximately 10% of patients lack driver mutations and are referred as ‘triple-negative’ ET (TN-ET). The diagnosis of TN-ET, however, relies on bone marrow examination that is not always performed in routine practice, and thus in the real-world setting, there are a group of cases with suspected TN-myeloproliferativeneoplasm.

In this real-world cohort, patients with suspected TN-ET were initially rescreened forJAK2,CALRandMPLand then targeted next-generation sequencing (NGS) was applied.

The 35 patients with suspected TN-ET had a median age at diagnosis of 43 years (range 16–79) and a follow-up of 10 years (range 2–28). The median platelet count was 758×109/L (range 479–2903). Thrombosis prior to and following diagnosis was noted in 20% and 17% of patients. Six patients wereJAK2V617F and two patients wereCALRpositive on repeat screening. NGS results showed that 24 of 27 patients harboured no mutations. Four mutations were noted in three patients.

There was no evidence of clonality for the majority of patients with suspected TN-ET with targeted NGS analysis. Detection of driver mutations in those who were previously screened suggests that regular rescreening is required. This study also questions the diagnosis of TN-ET without the existence of a clonal marker.
Potential impact of eliminating illicit trade in cigarettes: a demand-side perspective
Authors: Goodchild Mark , Paul Jeremias , Iglesias Roberto , Bouw Annerie , Perucic Anne-Marie
Published: November 2020

Background

The Protocol to Eliminate Illicit Trade in Tobacco Products (the Protocol) entered into force in September 2018, and commits Parties to implement a package of measures to combat this global problem. The aim of this study is to assess the potential impact of eliminating illicit cigarettes on consumption, use and tax revenues.

Methods

We identified 36 countries where an independent (non-industry sponsored) study of the illicit cigarette market was available. We developed a conceptual framework for describing how the elimination of illicit cigarettes might impact on demand (consumption and use) and applied this framework to our sample of countries to assess the impact of eliminating illicit cigarettes across different settings.

Findings

Illicit cigarettes account on average for 11.2% of the market in these 36 countries. The elimination of illicit cigarettes would reduce total cigarette consumption by 1.9% across these countries. The decrease in ‘group A’ countries—where illicit cigarettes are >15% of the market—would average 4.1%. The smoking rate would decrease by 1.0% in relative terms including by 2.2% in group A countries. Tax revenues from the legal sale of cigarettes would increase by 11.2% including by 25.1% in group A countries.

Conclusions

The illicit cigarette market reflects a complex interplay between supply and demand, with an array of different country conditions. Regardless of the situation, our study highlights the contribution that the elimination of illicit trade can make to tobacco control through demand reduction while at the same time generating significant tax revenues.