bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel, Open-Source, Low-Cost Bioreactor for Load-Controlled Cyclic Loading of Tendon Explants
Authors: Pedaprolu Krishna , Szczesny Spencer E.
Published: February 2022

A major risk factor for tendinopathy is tendon overuse (i.e., fatigue loading). Fatigue loading of tendon damages the extracellular matrix and induces tissue degeneration. However, the specific mechanisms linking tendon fatigue damage with tissue degeneration are unclear. While explant models of tendon fatigue loading have been used to address this knowledge gap, they predominantly employ bioreactors that apply cyclic displacements/strains rather than loads/stresses, which are more physiologically relevant. This is because of the technical complexity and cost of building a load-controlled bioreactor, which requires multiple motors, load cells, and computationally intensive feedback loops. Here, we present a novel, low-cost, load-controlled bioreactor that applies cyclic loading to multiple tendon explants by offloading weights from a single motorized stage. Using an optional load cell, we validated that the bioreactor can effectively provide load-controlled fatigue testing of mouse and rat tendon explants while maintaining tissue viability. Furthermore, all the design files, bill of materials, and operating software are available “open source”1 so that anyone can easily manufacture and use the bioreactor for their own research. Therefore, this novel load-controlled bioreactor will enable researchers to study the mechanisms driving fatigue-induced tendon degeneration in a more physiologically relevant and cost-effective manner.
The Elephant in the Cell: Nuclear Mechanics and Mechanobiology
Authors: Jones Michelle L. , Dahl Kris Noel , Lele Tanmay P. , Conway Daniel E. , Shenoy Vivek , Ghosh Soham , Szczesny Spencer E.
Published: February 2022

The 2021 Summer Biomechanics, Bioengineering, and Biotransport Conference (SB3C) featured a workshop titled “The Elephant in the Room: Nuclear Mechanics and Mechanobiology.” The goal of this workshop was to provide a perspective from experts in the field on the current understanding of nuclear mechanics and its role in mechanobiology. This paper reviews the major themes and questions discussed during the workshop, including historical context on the initial methods of measuring the mechanical properties of the nucleus and classifying the primary structures dictating nuclear mechanics, physical plasticity of the nucleus, the emerging role of the linker of nucleoskeleton and cytoskeleton (LINC) complex in coupling the nucleus to the cytoplasm and driving the behavior of individual cells and multicellular assemblies, and the computational models currently in use to investigate the mechanisms of gene expression and cell signaling. Ongoing questions and controversies, along with promising future directions, are also discussed.
A Free-Standing, Silent, Micro/Mesoscale Combustion-Powered Thermoelectric Generator Based on Natural Convection Cooling
Authors: Tulu Mikiyas Bekele , Li Guoneng , Alemayehu Dawit Bogale , Yi Minbo
Published: February 2022

In recent years, the world has become increasingly interested in power generation using thermoelectric generators (TEG) because of the advantage of converting heat directly to electricity. In this work, experimental studies have been carried out on micro/mesoscale combustor-powered thermoelectric generators (MCP-TEG) to evaluate the influence of different types of heat sinks on the cold side of MCP-TEG. The micro/mesoscale combustor was connected with Bi2Te3 based TEG1-12708 thermoelectric modules from both sides along with a heat sink on the cold side of the modules. The system uses natural convection cooling with a flat-plate aluminum heat sink. The MCP-TEG generates electrical power of 0.242 W with an overall efficiency of 0.3% at a hot-end temperature of 351 K. Power load feature and time history tests are conducted to evaluate the performance of the MCP-TEG system and comparisons of various related studies were made.
Wind Tunnel Investigation and Numerical Analysis of Fume Behavior in the Vicinity of Rectangular Building Under Moderate Velocity Wind
Authors: Mahjoub Hammouda , Abdulkadhim Ammar , Ben Romdhane Sahar , Mahjoub Said Nejla , Bournot Hervé , Mejbel Abed Isam
Published: February 2022

A research was conducted to examine the dispersion of pollutants ejected from a chimney around three-dimensional rectangular building. Regarding the experimental study, the wind tunnel experiment comprises data acquired through the dispersion of continuous source tracer discharges from a punctual source situated in a regular network of building-like obstacle, and these data include measurements of mean velocity and turbulence parameters. The relevant data are followed using Particle Image Velocimetry to track various instantaneous and mean dynamic characteristics. Concerning the numerical study, the suggested model simulates both the dynamics and the heat transfer flow field using the overall mean three-dimensional Navier-Stokes equations with an RSM turbulence closure model. The findings of a deep comparison of turbulent flow and dispersion between a full wind tunnel experiment and the model predictions are reported. A high degree of concordance was obtained with the experimental flow and numerical simulation data. The detailed investigation, in which numerical and wind tunnel studies, was performed to evaluate the impact of wind velocity on the pollutant dispersion issued from a chimney around the building in their vicinity. the results clearly showed how wind velocity influenced the environmental air flows and pollutant dispersal pathways. The results of this study show that the shape of the building and the resulting interaction between the wind structure play a determining factor in the distribution of pollutants around a building, thereby affecting the air quality in the various parts of the building.
Experimental Investigation of the Pre-Stall and Stall Evolution in a Centrifugal Compressor With a Volute
Authors: Zhang Hanzhi , Yang Ce , Wang Wenli , Yang Changmao , Li Yanzhao
Published: February 2022

Stall and surge behaviors deteriorate the compressor performance and stability of the operating range. To avoid the effect of stall and surge behaviors, the characteristics of the pre-stall disturbance have been considered in recent years. However, investigations of the pre-stall and stall disturbances in centrifugal compressors remain insufficient owing to the various geometric structures in centrifugal compressors. In this study, a centrifugal compressor with a volute and vaneless diffuser was studied using high-response static pressure measurements and numerical simulations. The pressure disturbance evolution from near-choke to near-surge conditions was obtained, and the characteristics of the pre-stall and stall disturbances were analyzed. The results showed that the compressor instability route could be divided into pre-stall and stall stages, which could be accurately predicted based on the periodic static pressure irregularity and skewness. The pre-stall stage was dominated by the rotating instability (RI) phenomenon, and the frequency of the RI was 43% of the blade passing frequency at 70% Nmax. The experimental results demonstrated that the first onset of RI occurred at the 120 deg–180 deg circumferential position and maintained a local pattern; then, RI occurred over the whole annulus when the flowrate was decreased. RI was induced by the vortex structure attached to the casing wall, leading to a sharp pressure trough in the static pressure trace. The RI exhibited an evolution pattern of initially increasing and then fading, which can be explained by the enlargement and movement of the impeller inlet vortex. The large blockage effect of RI triggered a stall with disturbances at 20% and 80% of the impeller shaft frequency, and these disturbance frequencies had a trend of shifting to one dominant frequency of 22% the impeller shaft frequency. Furthermore, stall cell merging and the coexistence of RI/stall phenomena occurred during the stall stage.
A Microinjector Free of Satellite Drops and Characterization of the Ejected Droplets
Authors: Tseng Fan-Gang , Kim Chang-Jin “CJ” , Ho Chih-Ming
Published: February 2022

This paper presents the droplet characteristics of a newly developed thermally driven microinjector, which uses asymmetric bubbles to increase the injection frequency significantly. Through special heater and chamber design, bubbles are generated to surround the nozzle in such a way to cut off the droplet tail and eliminate satellite droplets. Visualization systems are developed to verify the droplet ejection free of satellite droplets and to characterize the ejection and trajectory. A simple Stokes-flow model is also used to estimate the droplet ejection trajectory.
A Simple and Flexible Micro Reactor for Investigations on Heterogeneous Catalytic Gas Phase Reactions
Authors: Veser G. , Friedrich G. , Freygang M. , Zengerle R.
Published: February 2022

Micro reactors, i.e. chemical reactors with characteristic dimensions in the sub-millimeter range, hold great promise for novel chemical process routes (Lerou 1996, Wengeng 1996). Among their potential advantages for chemical processes are: the very small thermal inertia, allowing for a very direct control of temperature as a very critical reaction parameter; their inherent safety due to both the small reactant volume being present at any time in the reactor and the well controllable reactor and reaction conditions; and their small dimensions, making them easy to integrate into existing processes or to use them where space requirements are critical. Furthermore, for heterogeneously catalysed gas phase reactions, micro reactors offer the additional advantage of allowing for a very large surface to volume ratio. This should at least theoretically allow for an effective suppression of homogeneous gas phase reactions, since free surfaces typically are strong sinks for radical species which are required to keep the homogeneous reaction alive. Therefore, it should be possible to conduct a heterogeneously catalysed reaction involving a mixture of potentially flammable (if not explosive) gases in a micro reactor without any danger of open flames and explosion. This has the two-fold advantage, that not only the reaction becomes intrinsically safe, but it should also be possible to study heterogeneously catalysed high-temperature reactions without influences by parallel homogeneous reaction Pathways, making it a very valuable tool for research into this class of reactions.
Design, Testing, and Simulation of Microscale Gas Chromatography Columns
Authors: Hudson Mary L. , Kottenstette Richard , Matzke Carolyn M. , Frye-Mason Greg C. , Shollenberger Kim A. , Adkins Doug R. , Wong C. Channy
Published: February 2022

A microscale gas chromatography column is one component in a microscale chemistry laboratory for detecting chemical agents. Several columns were fabricated using the Bosch etch process which allows deep, high aspect ratio channels of rectangular cross-section. A design tool, based on analytical models, was developed to evaluate the effects of operating conditions and column specifications on separation resolution and time. The effects of slip flow, channel configuration, and cross-sectional shape were included to evaluate the differences between conventional round, straight columns and the microscale rectangular, spiral columns. Experimental data were obtained and compared with the predicted flowrates and theoretical number of plates. The design tool was then employed to select more optimum channel dimensions and operating conditions for high resolution separations.
Modification of Golay’s Theory for Rectangular Microfabricated Gas Chromatographic Columns
Authors: Spangler Glenn E.
Published: February 2022

The effect of band broadening in gas chromatography is specified by the height-equivalent-to-a-theoretical-plate (HETP) for the column. The HETP takes into account both longitudinal diffusion and resistance-to-mass-transfer in the gas and liquid phases. The original theory supporting HETP calculations was developed by Golay in 1958. Golay developed his theory for open-tubular and square columns, but not rectangular columns. This paper describes modifications that can be applied to Golay’s theory to address band broadening in a microfabricated rectangular column. For a given column length, microfabricated columns can have lower HETP’s than conventional capillary columns. A good rule of thumb is that resolution can be adjusted by selecting the column depth (provided it is much less than the column width), and the volumetric flow of carrier gas can be adjusted by selecting the cross-sectional area. A satisfactory compromise for operating parameters is to use a low inlet pressure that also provides an HETP that remains constant over a range of pressures.
Experimental Characterization of Printed Circuit Board-Based Cantilever Air Valves
Authors: Cheung Patrick , Berlin Andrew A. , Biegelsen David K. , Jackson Warren B. , Lau Rachel
Published: February 2022

In recent years there has been an emerging interest in the design, fabrication, and application of distributed air valves. Electrostatic cantilever air valves that are fabricated within a PC board process offer advantages such as low cost fabrication and potential for system integration. This paper reports on the operation and dynamics of these PCB valves. The experimental work focused on valve parameters such as cantilever flap size, material, thickness, orifice size, and dielectric thickness. Certain combinations of parameters were examined for real world operation including their flow handling capacity, switching speeds, voltage requirements, and durability. Valves that were fabricated in this work could switch in milliseconds, undertake hold-back pressures of over 2 KPa, and switch flows of over 6 SCFH. The hysteretic switching behavior is suitable for passive matrix addressing of arrays of such valves. Lifetimes exceeding 1 million cycles have been demonstrated.
Simulation and Design of Electro-Thermally Actuated MEMS Devices: A Case Study — The AFIT Piston Micromirror
Authors: Ghaddar Chahid K. , van Kuijk Joost , Gilbert John R. , Cowan William D. , Butler Jeffrey T. , Bright Victor M.
Published: February 2022

A finite element model has been developed using MEMCAD4.0 for the AFIT electrothermally actuated piston micromirror fabricated in the MCNC MUMPs 17 run. The model is used to quantify the residual stress in the mirror metal reflector and to simulate the mirror deflection and curvature both in vacuum and in nitrogen ambient. The numerical results are in good agreement with the measured values. The model is also used to predict the effect of the residual stress in the mirror supporting legs on the mirror deflection.
Genetic Algorithms in MEMS Synthesis
Authors: Li Hui , Antonsson Erik K.
Published: February 2022

Initial results have been obtained for automatic synthesis of MEMS mask-layouts using a genetic algorithm. An initial random population of mask-layouts is produced. An initial fabrication process sequence is also generated. The fabrication of each geometrically valid layout is simulated using a 3-D simulation of etching. The 3-D results of the fabrication simulation are compared to the desired 3-D shape. Resulting 3-D shapes that are determined to be sufficiently close to the desired shape are kept in the candidate population. A genetic algorithm is applied to each member of the remaining population of mask-layouts (and fabrication processes) to introduce random shape (and process) variations. The procedure is then repeated until one or more simulated shape is sufficiently close to the desired shape to stop the iteration.
Integrated Modeling and Testing of a Micro Hinged Structure for Sliding Friction Measurement
Authors: Redmond James M. , de Boer Maarten P. , Michalske Terry A.
Published: February 2022

This paper summarizes the design, modeling, and initial evaluation of a hinged structure for friction measurement in surface micromachining technology. While the area requirements are small, the present structure allows a much larger velocity and pressure range to be evaluated as compared to comb drive structures. The device consists of a cantilevered driver beam connected to a friction pad through a strategically located hinge. AC excitation of the beam flexure forces axial sliding of the friction pad due to beam foreshortening. Normal force is controlled by DC voltage on wings adjacent to the friction pad. While the achievable slip is small (10–30 nm), it is sufficient to disengage contacting asperities and engage new points of contact, and thus should be representative of frictional processes. Furthermore, the design enables the friction pad contact area to remain relatively constant over the excitation cycle. Computer simulation results are provided to mimic on-going experimental work. Increased friction forces are shown to enhance the size of hysteresis loops relating beam deflection to driver voltage.
Contact Resistance Modeling and Measurements of an Electrostatically Actuated Micromechanical Switch
Authors: Majumder Sumit , McGruer N. E. , Zavracky Paul M. , Morrison Richard H. , Adams George G. , Krim Jacqueline
Published: February 2022

An electrostatically actuated, surface micromachined microswitch is being developed and tested in the Microfabrication Laboratory at Northeastern University. In its simplest form, the microswitch consists of a nickel cantilever beam (approximately 70 :m long, 30 :m wide, and 2 :m thick), and three electrical terminals (made of gold), analogous to the drain, source and gate of an FET. Application of an actuating voltage between the gate electrode and the beam pulls the beam down so that the free end makes contact with the drain. The beam is fabricated with two or more miniature bumps at its end, with the objective of concentrating the contact force over a small area. The contact bump has a thin coating of electroplated gold creating a gold-on-gold electrical contact. Devices fabricated so far, have demonstrated threshold voltages of less than 30 V, long switching life (> 109 switch cycles in a nitrogen ambient), low on-resistance (< 1 ohm contact resistance), while carrying currents of 10 mA. The off-impedance exceeds 1012 Ohm. One of the primary objectives at this point is to understand the contact resistance characteristics. Contact resistance measurements are presented and compared with the results of a multi-asperity contact model of contact resistance.
Design and Fabrication of Piezoresistive Cantilever Microaccelerometer Arrays With a Symmetrically Bonded Proof-Mass
Authors: Ko Jong Soo , Cho Young-Ho , Kwak Byung Man , Park Kwanhum
Published: February 2022

This paper presents the production-oriented design and microfabrication process of a piezoresistive cantilever-beam microaccelerometer with a symmetrically bonded proof-mass. The symmetrically bonded proof-mass structure is devised not only for improving the production yield, but also for reducing the transverse sensitivity of the accelerometer. The accelerometers are batch fabricated in arrays, from which individual devices are obtained by wafer sawing process. The microfabricated accelerometer shows a resonant frequency of 2.15kHz and a sensitivity of 34μV/g/V within a nonlinearity of 2% over ±30g range at 100Hz. The structure and fabrication processes of the present accelerometer provide practical and effective means for the mass production of accelerometers with high reproducibility.
Utilization of Standard CMOS Layers for Microchannels
Authors: Rasmussen Angela , Locascio Laurie E. , Gaitan Michael , Zaghloul Mona E.
Published: February 2022

In this paper we describe two different methods to create microchannels using the standard CMOS integrated circuit process. Two different types of channels are demonstrated. One channel is surface micromachined to create a small depth channel. The other channel is bulk micromachined to realize a large depth channel. Each channel can have variable length and width. The shallow channel has a fixed depth that is dependent on the thickness of the standard metal layers in CMOS. The larger depth channel is controllable with a minimum depth of 30μm. The advantage of this process is that sensors, actuators, and electronics are very easily integrated with the microchannels.
A High Performance Hand-Held Gas Chromatograph
Authors: Yu Conrad M. , Lucas Matthew , Koo Jackson C. , Stratton Paul , DeLima Terri , Behymer Elaine
Published: February 2022

The Microtechnology Center of Lawrence Livermore National Laboratory has developed a high performance hand-held, real time detection gas chromatograph (HHGC) by Micro-Electro-Mechanical-System (MEMS) technology. The total weight of this hand-held gas chromatograph is about 5 lbs., with a physical size of 8″ × 5″ × 3″ including carrier gas and battery. It consumes about 12 watts of electrical power with a response time on the order of one to two minutes. This HHGC has an average effective theoretical plate of about 40k. Presently, its thermal sensitive detector at PPM limits its sensitivity.

Like a conventional G.C., this HHGC consists mainly of three major components: 1) the sample injector, 2) the column, and 3) the detector with related electronics. The present HHGC injector is a modified version of the conventional injector. Its separation column is fabricated completely on silicon wafers by means of MEMS technology. This separation column has a circular cross section with a diameter of 100 μm. The detector developed for this hand-held G.C. is a thermal conductivity detector fabricated on a silicon nitride window by MEMS technology. A normal Wheatstone bridge is used. The signal is fed into a PC and displayed through LabView software.
Design, Fabrication and Optical Characterization of Micro Fresnel Zone Plates
Authors: Lee Wen-Hong , Lin Liwei
Published: February 2022

Design, fabrication and optical characterization of micro Fresnel Zone Plates (FZP) are successfully demonstrated. These micro FZPs are composed of circular rings that have a maximum size of 9.4 mm in diameter and a minimum ring width of 2 μm. The absorber material is sputtered tungsten with a thickness of 0.5 μm that is deposited on top of a 2.5 μm thick low-stress nitride membrane. An optical system that is composed of a He-Ne laser, a pin-hole, various lenses and a CCD camera, is setup to measure the optical characteristics of micro FZPs. It is found that the relative intensity can be magnified about 100% higher by using these FZPs. These FZPs are powerful tools for forming images in the spectral region of infrared light, X- and gamma-rays where regular glass lenses can not be functional.
An 8x8 Robust Capacitive Pressure Sensor Array
Authors: Chang Sung-Pil , Lee Jeong-Bong , Allen Mark G.
Published: February 2022

In this work, robust substrates, such as stainless steel, have been studied as substrates for micromachined devices. The use of robust substrates may allow for the co-fabrication of micromachined devices and sensor packages. Lamination process techniques combined with traditional micromachining processes have been investigated as suitable fabrication technologies. To illustrate these principles, a capacitive pressure sensor array has been designed, fabricated, and characterized using a stainless steel substrate, Kapton polyimide film as a suspended movable plate, and an electroplated nickel fixed back electrode. The net capacitance change of this sensor over the applied pressure range (0 to 34 kPa) was approximately 0.14 pF. Multivibrator circuitry has been integrated with pressure sensors in a hybrid fashion and used for frequency-modulated output measurements. An important attribute of this design is that only the steel substrate and the pressure sensor inlet is exposed to the flow; i.e., the sensor is self-packaged.
MemCel: An Inexpensive and Efficient Tool for 3D MEMS Prototyping
Authors: Emmenegger Markus , Korvink Jan G. , Baltes Henry
Published: February 2022

We present a fast prototyping tool for the 3D visualisation and subsequent finite element simulation of 3D CMOS micro-electro-mechanical systems (MEMS). Our process emulation method takes as input the 2D mask layout in CIF format, together with the corresponding process description, and generates a cell representation of the 3D device. The cell representation correctly reflects the layer structure of the device in the direction perpendicular to the wafer surface. Our emulation tool MemCel currently runs in the Mathematica environment, enabling the efficient conversion of 2D design data to 3D representation good for visualisation and simulation. We illustrate the technique for typical surface micromachined and interconnect devices.
MEMS Opportunities in the Automotive Industry
Authors: Sickafus Ed
Published: February 2022

For nearly two decades the automobile industry has watched the MEMS area in anticipation of exciting new products with greater functionality and higher reliability. Considering the long development time that has ensued, it is a bit of a disappointment to see the limited adaptation of MEMS devices in automobiles to date. Examination of this situation points up some of the difficulties of meeting the needs of the industry for automotive sensors and actuators. A distinction that needs to be made to understand the problem is the distinction between MEMS potential for automotive applications and actual adaptation of MEMS. The potential for MEMS automotive applications will be examined first, then the actual successes will be discussed. Lastly, reasons for the limited successes of automotive-type MEMS will be examined. This will bring out some needs for new direction as well as needs to understand business decisions and MEMS comptetition.
Operationally Focused Management of Pumps in Alert: Using Analysis to Remove a High Pressure Safety Injection Pump From Increased-Frequency Test Schedule
Authors: Arnold Eli
Published: February 2022

Pressurized water reactor designs preclude full-flow testing of certain safety-related standby pumps during power operations. This is problematic for Group B pumps that test in the alert range under comprehensive pump test conditions that are only available during refueling outages. The ASME OM committees sought to resolve this issue when new provisions were added to ISTB-6200 in ASME OM-2012. The provisions allow analysis of pump performance in lieu of testing at an increased frequency. Palo Verde Generating Station employed these rules to satisfy OM requirements for a vibration alert range entry of its high pressure safety injection pump without having to submit for regulatory relief or shut down to perform the test. The changes to ISTB-6200 in ASME OM-2012 give plants the flexibility to ensure safe operation without undergoing extraordinary measures to accommodate testing requirements.
Augmented IST Program Requirements – Scope and Testing
Authors: Gowin Mark
Published: February 2022

The purpose of this presentation is to raise awareness on the requirements in 10 CFR 50.55a(f) (4) for development and implementation of an Augmented IST Program. This presentation will highlight the changes in 10 CFR 50.55a rulemaking that changed the scope of the regulatory required IST Program to include all safety related components regardless of their site specific ASME Code Class equivalent classification. This presentation will also describe the available options to address those components classified as ASME Code Class 1, 2, or 3 equivalent versus those that are not classified as ASME code equivalent which also meet the scope statement of ASME OM Code, ISTA-1100.
Prevalence and Correlates of Insufficient Physical Activity Among Adults Aged 18–69 Years in India: Findings From the National Noncommunicable Disease Monitoring Survey
Authors: Ramamoorthy Thilagavathi , Kulothungan Vaitheeswaran , Mathur Prashant
Published: February 2022

Background: Sufficient physical activity (PA) significantly contributes to the prevention and control of noncommunicable diseases. This study aims to determine the prevalence of insufficient PA and associated sociodemographic and lifestyle factors among adults aged 18–69 years in India. Methods: A national population-based, cross-sectional survey was conducted during 2017–2018 among 12,000 adults that adapted globally standard data collection tools. The data were weighted and analyzed using complex samples analysis. Logistic regression analysis was performed to identify the sociodemographic and lifestyle factors associated with insufficient PA. Results: Age standardized prevalence of insufficient PA among adults in India was 41.4%. A higher proportion of women (52.4%) and urban adults (51.7%) were not doing sufficient PA. Men (118.8 min) spent more time in PA per day than women (55.3 min). Higher odds of insufficient PA were significantly associated with unemployment (adjusted odds ratio [aOR] = 6.45), highest wealth quintile (aOR = 1.86), presence of central obesity (aOR = 1.24), and raised blood pressure (aOR = 1.22). Conclusion: This study provides the baseline prevalence of insufficient PA to monitor the set PA targets for India by 2025. The identified associated factors can guide policy makers to plan tailored interventions targeting high-risk groups and a multisectoral approach to promote PA.
Forgetting generates a novel state that is reactivatable
Authors: Liu He , Wu Taihong , Canales Xicotencatl Gracida , Wu Min , Choi Myung-Kyu , Duan Fengyun , Calarco John A. , Zhang Yun
Published: February 2022

Forgetting is defined as a time-dependent decline of a memory. However, it is not clear whether forgetting reverses the learning process to return the brain to the naive state. Here, using the aversive olfactory learning of pathogenic bacteria in
C. elegans
, we show that forgetting generates a novel state of the nervous system that is distinct from the naive state or the learned state. A transient exposure to the training condition or training odorants reactivates this novel state to elicit the previously learned behavior. An AMPA receptor and a type II serotonin receptor act in the central neuron of the learning circuit to decrease and increase the speed to reach this novel state, respectively. Together, our study systematically characterizes forgetting and uncovers conserved mechanisms underlying the rate of forgetting.
Structural origins of cartilage shear mechanics
Authors: Wyse Jackson Thomas , Michel Jonathan , Lwin Pancy , Fortier Lisa A. , Das Moumita , Bonassar Lawrence J. , Cohen Itai
Published: February 2022

Articular cartilage is a remarkable material able to sustain millions of loading cycles over decades of use outperforming any synthetic substitute. Crucially, how extracellular matrix constituents alter mechanical performance, particularly in shear, remains poorly understood. Here, we present experiments and theory in support of a rigidity percolation framework that quantitatively describes the structural origins of cartilage’s shear properties and how they arise from the mechanical interdependence of the collagen and aggrecan networks making up its extracellular matrix. This framework explains that near the cartilage surface, where the collagen network is sparse and close to the rigidity threshold, slight changes in either collagen or aggrecan concentrations, common in early stages of cartilage disease, create a marked weakening in modulus that can lead to tissue collapse. More broadly, this framework provides a map for understanding how changes in composition throughout the tissue alter its shear properties and ultimate in vivo function.
BMFPs, a versatile therapeutic tool for redirecting a preexisting Epstein-Barr virus antibody response toward defined target cells
Authors: Gamain Benoît , Brousse Carine , Rainey Nathan E. , Diallo Béré K. , Paquereau Clara-Eva , Desrames Alexandra , Ceputyte Jolita , Semblat Jean-Philippe , Bertrand Olivier , Gangnard Stéphane , Teillaud Jean-Luc , Chêne Arnaud
Published: February 2022

Industrial production of therapeutic monoclonal antibodies is mostly performed in eukaryotic-based systems, allowing posttranslational modifications mandatory for their functional activity. The resulting elevated product cost limits therapy access to some patients. To address this limitation, we conceptualized a novel immunotherapeutic approach to redirect a preexisting polyclonal antibody response against Epstein-Barr virus (EBV) toward defined target cells. We engineered and expressed in bacteria bimodular fusion proteins (BMFPs) comprising an Fc-deficient binding moiety targeting an antigen expressed at the surface of a target cell, fused to the EBV-P18 antigen, which recruits circulating endogenous anti-P18 IgG in EBV
+
individuals. Opsonization of BMFP-coated targets efficiently triggered antibody-mediated clearing effector mechanisms. When assessed in a P18-primed mouse tumor model, therapy performed with an anti-huCD20 BMFP significantly led to increased survival and total cancer remission in some animals. These results indicate that BMFPs could represent potent and useful therapeutic molecules to treat a number of diseases.
A programmable high-expression yeast platform responsive to user-defined signals
Authors: Liu Qi , Song Lili , Peng Qiangqiang , Zhu Qiaoyun , Shi Xiaona , Xu Mingqiang , Wang Qiyao , Zhang Yuanxing , Cai Menghao
Published: February 2022

Rapidly growing yeasts with appropriate posttranslational modifications are favored hosts for protein production in the biopharmaceutical industry. However, limited production capacity and intricate transcription regulation restrict their application and adaptability. Here, we describe a programmable high-expression yeast platform, SynPic-X, which responds to defined signals and is broadly applicable. We demonstrated that a synthetic improved transcriptional signal amplification device (iTSAD) with a bacterial-yeast transactivator and bacterial-yeast promoter markedly increased expression capacity in
Pichia pastoris
. CRISPR activation and interference devices were designed to strictly regulate iTSAD in response to defined signals. Engineered switches were then constructed to exemplify the response of SynPic-X to exogenous signals. Expression of α-amylase by SynPic-R, a specific SynPic-X, in a bioreactor proved a methanol-free high-production process of recombinant protein. Our SynPic-X platform provides opportunities for protein production in customizable yeast hosts with high expression and regulatory flexibility.
Asymmetric Notch activity by differential inheritance of lysosomes in human neural stem cells
Authors: Bohl Bettina , Jabali Ammar , Ladewig Julia , Koch Philipp
Published: February 2022

Symmetric and asymmetric cell divisions are conserved strategies for stem cell expansion and the generation of more committed progeny, respectively. Here, we demonstrate that in human neural stem cells (NSCs), lysosomes are asymmetrically inherited during mitosis. We show that lysosomes contain Notch receptors and that Notch activation occurs the acidic lysosome environment. The lysosome asymmetry correlates with the expression of the Notch target gene
HES1
and the activity of Notch signaling in the daughter cells. Furthermore, an asymmetry of lysosomes and Notch receptors was also observed in a human organoid model of brain development with mitotic figures showing preferential inheritance of lysosomes and Notch receptor in that daughter cell remaining attached to the apical membrane. Thus, this study suggests a previously unknown function of lysosomes as a signaling hub to establish a bias in Notch signaling activity between daughter cells after an asymmetric cell division of human NSCs.
Coriolis effect recorded in Late Pleistocene Marine Isotope Stage 5e Bahamian aeolianites
Authors: Rendall Ben , Wilson Kat , Kerans Charles , Helper Mark , Mohrig David
Published: February 2022

The windward islands of the Lucayan Archipelago (Bahamas) form an Atlantic Ocean–facing transect spanning >950 km in length and 6° of latitude. The islands' topography is largely constructed from carbonate wind-blown dunes (i.e., aeolianites) deposited during the interglacial phases of the Late Pleistocene and Holocene. New digital elevation data from satellite radar interferometry (TanDEM-X German Earth observation satellite) enables a step change in the ability to map and quantify Bahamian aeolian landforms across the archipelago. A semi-automated mapping approach that leverages object-based image analysis yields a total aeolianite area of ~1674 km2 across Great Abaco, Eleuthera, Cat, San Salvador, Long, Crooked, Acklins, and Mayaguana islands (Bahamas) and the Turks and Caicos Islands. Longitudinal axis measurements from 747 Pleistocene parabolic dunes record increasing consistency of east-west orientation with decreasing latitude. Three U.S. National Data Buoy Center data buoys provided modern wind direction and velocity measurements (n = 730,933 of each) along this transect. Analysis of wind vectors (>P90 [90th percentile], n = 70,095) demonstrates increasing organization of easterlies at southern latitudes and an offset in directionality compared to formational winds of Pleistocene Marine Isotope Stage (MIS) 5e deposits. Southward trends of increasing wind strength and consistency reflect geostrophic flow driven by atmospheric circulation within the Hadley cell and right-hand deflection of the Coriolis effect in the Northern Hemisphere. We propose that the offset in directionality between dune axes and modern wind vectors is related to changes in latitudinal width of the Hadley cell from the Late Pleistocene (MIS 5e) to today. This data set is robust enough to serve as a benchmark against which future atmospheric circulation models can be compared.
Assessing vaccine hesitancy in Arab countries in the Middle East and North Africa (MENA) region: a scoping review protocol
Authors: Galal Bayan , Lazieh Stefany , Al-Ali Samir , Khoshnood Kaveh
Published: February 2022

Introduction

Vaccine-preventable disease outbreaks have increased in past years, and there is great public health interest in monitoring attitudes towards vaccination as well as identifying factors contributing to vaccine hesitancy and refusal. Although the WHO declared vaccine hesitancy as one of the top threats to global health in 2019, studies focused on the determinants and extent of vaccine hesitancy in Arab countries in the Middle East and North Africa (MENA) region are lacking. This scoping review explores the various factors surrounding vaccine hesitancy, including but not limited to geographic, cultural and religious factors, and examines the extent and nature of the existing evidence on this topic. In light of current development of various COVID-19 vaccines, our work seeks to elucidate the barriers to vaccine uptake in specific populations.

Methods and analysis

This review will be conducted using the Joanna Briggs Institute Manual for Scoping Reviews. It will comply with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. Studies published in English, Arabic and French between January 1998 and December 2020 will be drawn from PubMed, Embase, Cochrane and Scopus. The search strategy will include terms related to vaccination and vaccine hesitancy in Arab countries in the MENA region. We will also include grey literature on the topic by searching Google and Google Scholar. Studies will be selected according to the Participants-Intervention-Comparators-Outcome model, and all study titles and abstracts will be screened by two reviewers. Disagreements will be resolved with a third reviewer’s input.

Ethics and dissemination

This review is exempted from ethical approval and will be published in a peer-reviewed open-access journal to ensure wide dissemination.
Protocol for an integrated evaluation framework to study training, curricular and contextual factors impacting the success of a measurement for improvement training programme for healthcare staff in Ireland
Authors: Khurshid Zuneera , De Brún Aoife , McAuliffe Eilish
Published: February 2022

Introduction

Measurement for improvement is the process of collecting, analysing and presenting data to demonstrate whether a change has resulted in an improvement. It is also important in demonstrating sustainability of improvements through continuous measurement. This makes measurement for improvement a core element in quality improvement (QI) efforts. However, there is little to no research investigating factors that influence measurement for improvement skills in healthcare staff. This protocol paper presents an integrated evaluation framework to understand the training, curricular and contextual factors that influence the success of measurement for improvement training by using the experiences of trainees, trainers, programme and site coordinators.

Methods and analysis

This research will adopt a qualitative retrospective case study design based on constructivist-pragmatic philosophy. The Pressure Ulcers to Zero collaborative and the Clinical Microsystems collaborative from the Irish health system which included a measurement for improvement component have been selected for this study. This paper presents an integrated approach proposing a novel application of two pre-existing frameworks: the Model for Understanding Success in Quality framework and the Kirkpatrick Evaluation Model to evaluate an unexplored QI context and programme. A thematic analysis of the qualitative interview data and the documents collected will be conducted. The thematic analysis is based on a four-step coding framework adapted for this research study. The coding process will be conducted using NVivo V.12 software and Microsoft Excel. A cross-case comparison between the two cases will be performed.

Ethics and dissemination

The study has received an exemption from full ethical review from the Human Research Ethics Committee of University College Dublin, Ireland (LS-E-19-108). Informed consent will be obtained from all participants and the data will be anonymised and stored securely. The results of the study will be disseminated in peer-reviewed journals.
Determinants of antenatal care use in nine sub-Saharan African countries: a statistical analysis of cross-sectional data from Demographic and Health Surveys
Authors: Andegiorgish Amanuel Kidane , Elhoumed Mohamed , Qi Qi , Zhu Zhonghai , Zeng Lingxia
Published: February 2022

Objective

To explore the factors associated with antenatal care (ANC) visits.

Design

A secondary data analysis from cross-sectional studies was conducted.

Setting

Sub-Saharan Africa.

Participants

56 002 women aged 15–49 years in Ghana (3224), Kenya (10 981), Malawi (9541), Namibia (2286), Rwanda (4416), Senegal (6552), Tanzania (5536), Uganda (7979) and Zambia (5487) were analysed.

Outcomes

4+ANC visits.

Results

Overall, 55.52% (95% CI: 55.11% to 55.93%) of women made 4+ANC visits. The highest 4+ANC visits were in Ghana (85.6%) and Namibia (78.9%), and the lowest were in Senegal (45.3%) and Rwanda (44.5%). Young women 15–19 years had the lowest uptake of 4+ANC visits. Multivariable analysis indicated that the odds of 4+ANC visits were 14% lower among women from rural areas compared with those living in towns (adjusted OR (AOR) 0.86; 95% CI: 0.81 to 0.91). This difference was significant in Kenya, Malawi, Senegal and Zambia. However, in Zambia, the odds of 4+ANC visits were 48% higher (AOR 1.48; 95% CI: 1.2 to 1.82) among women from rural compared with urban areas. Women with higher educational level had more than twofold higher odds of 4+ANC visits in seven of the nine countries, and was significant in Kenya, Malawi, Rwanda and Zambia. Compared with the poorest household wealth category, odds of 4+ANC visits increased by 12%, 18%, 32% and 41% for every 20% variation on the wealth quantile. Women in their first-time pregnancy had higher odds of 4+ANC visits compared with others across all countries, and women who had access to media at least once a week had a 22% higher probability of 4+ANC visits than women who had no access to media (AOR 1.22, 95% CI: 1.15 to 1.29).

Conclusion

The number of ANC visits was considered to be inadequate with substantial variation among the studied countries. Comprehensive interventions on scaling uptake of ANC are needed among the low-performing countries. Particular attention should be given to women of low economic status and from rural areas.
Comparison of dexmedetomidine and meperidine for the prevention of shivering following coronary artery bypass graft: study protocol of a randomised controlled trial
Authors: Cao Cuicui , Lv Meng , Wei Chuansong , Yan Jie , Wang Yuelan , Gu Changping
Published: February 2022

Introduction

Shivering is a common complication in the postoperative period. The incidence of shivering has been reported to range from 5% to 65% under general anaesthesia and as 33% during epidural anaesthesia. Shivering can increase perioperative risk in patients. Both dexmedetomidine and meperidine are effective agents for the prevention of postanaesthetic shivering. However, few studies have compared the anti-shivering effects of different agents following coronary artery bypass graft (CABG). This study aims to compare the effects of dexmedetomidine and meperidine on the incidence of shivering in patients undergoing CABG.

Methods and analysis

A total of 180 patients aged 18–75 years, with an American Society of Anesthesiologists (ASA) grade of II–IV, undergoing elective CABG will be enrolled and randomly assigned to the dexmedetomidine, meperidine and control groups (placebo) in an intended 1:1:1 allocation ratio. The patients will be followed up for 7 days after surgery. The primary outcome is the incidence of shivering within 24 hours postoperatively. The secondary outcomes are the number of remedial drugs used after surgery, the incidence of postoperative hypotension and bradycardia, sedation scores, endotracheal extubation time, intensive care unit length of stay, incidence of postoperative delirium within 7 days after surgery, incidence of postoperative arrhythmias, incidence of postoperative nausea and vomiting, average hospital length of stay and mortality rate 30 days after surgery.

Ethics and dissemination

The study protocol was approved by the ethics committee of The First Affiliated Hospital of Shandong First Medical University on 20 January 2021 (YXLL-KY-2021(002)) and registered at ClinicalTrials.gov. The results of this study will be presented at national and international scientific meetings and conferences. We plan to publish the data in peer-reviewed international scientific journals.

Trial registration number

NCT04735965.