bluuebunny/crossref_metadata_2025 huggingface dataset:
A MULTI-HEADED CNN FRAMEWORK FOR LAMB WAVE-BASED DAMAGE DETECTION IN A THIN ALUMINUM PLATE
Authors: RAI AKSHAY , MITRA MIRA
Published: October 2022

In this research, a deep learning framework of 1D-Convolutional neural networks (CNNs) is utilized to recognize and auto-extract damage related features within the fragments of raw 1-D Lamb wave data. To analyze the performance of the proposed network, a diverse database is constructed to train and test the 1D-CNN architecture. It contains Lamb waves time-series data recorded from both 24 experimental and 216 Finite Element (FE) simulation setups of 1.6 mm thin Al-5052 plate. To scan the platestructure, a pitch-catch transducers configuration is adopted. The actuator-transducer excites 3.5 cycles modulated sinusoidal tone-burst signal at three different frequencies i.e., 100 kHz, 125 kHz and 150 kHz and the corresponding responses are collected from sensor-transducer only. An anomaly is introduced in the FE model in the form of a 0.8 mm deep and 2 mm wide notch-like cavity. Whereas, the damage in the experimental setup is realized by attaching an external mass of 14 gm in the center of the PZTs. Next, a 1D-CNN architecture is designed that uses raw 1D Lamb wave signals as an input and can capture high-level damage related features from the raw Lamb wave signals. Then the CNN model is trained on 90% of the total number of samples in the database using the Adam algorithm. At a later stage, the trained 1D-CNN architecture performance is validated against the 24 unseen Lamb wave responses. Out of the 24 unseen samples, the proposed architecture decisively predicts the outcome for 23 samples. This test against the unseen experimentally generated samples proves that the proposed deep learning framework has achieved the required generalization over the real scenario.
LIGHTWEIGHT DEEP LEARNING MODEL OF SEMANTIC SEGMENTATION FOR COMPLEX CONCRETE CRACKS IN ACTUAL BRIDGE INSPECTION
Authors: XU YANG , FAN YUNLEI , QIAO WEIDONG , LI HUI
Published: October 2022

Recently, extensive studies have been performed for crack detection and segmentation using deep learning and computer vision techniques to accomplish autonomous bridge inspection. These deep network models are frequently trained with a large volume of parameters to ensure good performance. However, the robust applications under real-world situations of actual bridge inspection still face significant challenges. For example, false-positive recognitions of complex background disturbances excluded in the training sets are inevitable to exist. Besides, the real-time requirement for deploying large-volume deep networks in edge computing equipment is still challenging to achieve. This study establishes a lightweight semantic segmentation model for complex concrete crack segmentation in actual bridge inspection. First, the DeepLabv3+ model is adopted as the baseline, and the backbone module is replaced by MobileNetV2 instead of ResNet101. Second, the depthwise separable convolution, atrous convolution pyramid, and inverted residual modules are utilized to reduce convolutional parameters, expand receptive fields, and alleviate gradient vanishing, respectively. Third, the dataset is enhanced with negative disturbance examples, including straight-line-like structural edges and exposed rebars, to improve the model performance against false positives without additional labeling workload. Original images with different resolutions are first collected from actual bridges, and negative samples are further added to the dataset. A total of 4303 patches in 512 × 512 are generated by a sliding window, where 3443, 430, and 430 are randomly selected for training, validation, and test. Ablation experiments demonstrate the necessity and effectiveness of using MobileNetV2 instead of ResNet101 as the backbone and adding negative examples into the dataset. The results show that the mean intersection-over-union (mIoU) for crack segmentation in various real-world scenarios reaches 0.759. The recognition rate of false positives for complex background disturbances is effectually suppressed by introducing straight-line-like structural edges and exposed rebars into the dataset. Furthermore, the average time cost gains a significant reduction of 35.1% using the established lightweight crack segmentation model with only a slight drop on IoU of 0.017.
NATURAL SYNCHRONIZATION OF WIRELESS SENSOR NETWORKS FOR STRUCTURAL HEALTH MONITORING
Authors: ŠILJAK HARUN , BASU BISWAJIT
Published: October 2022

Time synchronization in communication networks is a common issue: in a sensor network it means that the order of data samples becomes uncertain, which can make it unusable. Dedicated signals and schemes for synchronization of sensor networks has hence been a well-researched topic for decades. Here we bring in an approach to synchronization which uses the sensory data. Drawing inspiration from sensor time synchronization using environmental noise, we consider synchronizing sensory nodes for structural health monitoring–if the physical quantity the sensors measure is correlated, propagating as a wave, or oscillating in regular fashion, it is intuitively clear how to put it to use. We discuss when structural health monitoring signals can aid synchronization; we also connect this synchronization scheme to the idea of using physical human-made structures as reservoirs for reservoir computing, formulating synchronization as a reservoir computing task.
Accelerability vs. Scalability: R&D Investment Under Financial Constraints and Competition
Authors: Lin Danmo
Published: October 2022

I develop a continuous-time model to examine how the interaction between competition and financial constraints affects firms’ research and development (R&D) strategies. The model integrates two key characteristics of R&D investment: accelerability (i.e., higher R&D intensity leads to faster discovery) and scalability (i.e., higher R&D intensity leads to higher project payoff). I find that firms react strategically to their rivals’ financial constraints when making investment decisions in a duopoly R&D race. In particular, firms respond positively to the R&D intensity of an unconstrained rival, while they respond in a hump-shaped fashion to the R&D intensity of a constrained rival. As a result, a constrained firm can pre-empt an unconstrained competitor in market equilibrium. Accelerability is necessary for such pre-emption to occur, and scalability generally reduces its likelihood. Comparison with a monopoly benchmark shows that the economic mechanism differs from over-investment induced by financial constraints alone. The model also generates new implications regarding how project characteristics and cash flow risks impact R&D decisions.

This paper was accepted by Gustavo Manso, finance.

Supplemental Material: The online appendix is available at https://doi.org/10.1287/mnsc.2022.4503 .
Early discontinuation of Implanon and associated factors among women in public health facilities of the Hawassa administration, south Ethiopia
Authors: Reda Mulu , Abebe Belay Amare
Published: October 2022

Background/Aims

Despite improving availability and use of the contraceptive Implanon, early discontinuation is a public health concern. A significant proportion of women discontinue using Implanon before it is due to be removed, which poses a health concern and may lead to contraceptive failure. Only 8% of married women in Ethiopia use contraceptive implants. There is a paucity of information on factors associated with early discontinuation of Implanon. This study's aims were to assess early discontinuation of Implanon and associated factors among women using public health facilities of Hawassa, south Ethiopia.

Methods

An institution-based cross-sectional study was conducted in six randomly selected public health facilities in Hawassa. All women using Implanon who visited the selected institutions during the data collection period were invited to participate in the study. Data were collected through face-to-face interviews using a pretested questionnaire. A multivariate logistic regression model was used to identify predictors of early Implanon removal.

Results

Of the 250 study participants, 54.0% discontinued using Implanon early. A woman having primary level education (adjusted odds ratio=2.332, P=0.048), lack of counselling about the possible benefits of Implanon (adjusted odds ratio=2.496, P=0.019), side effects (adjusted odds ratio=2.092, P=0.002) and the desire to be pregnant in the near future (adjusted odds ratio=2.222, P<0.0001) were associated with early discontinuation.

Conclusions

Over half of women using Implanon discontinued early, which was related to lower education, a lack of counselling, side effects of the implant and the desire to become pregnant. Pre-insertion counselling for women should include information on the possible side effects and benefits of Implanon, to decrease the proportion of women who discontinue its use early.
Compassionate and respectful maternity care for mothers who gave birth in public health facilities in North Gondar, Ethiopia: a cross-sectional study
Authors: Zeleke Agerie Mengistie , Bayeh Gashaw Melkie
Published: October 2022

Background

Improving the prevalence of compassionate and respectful maternity care is a critical agenda and an important component of healthcare provider quality assurance. Making compassionate and respectful maternity care available is an important way to increase facility-based childbirth use in Ethiopia. However, evidence on compassionate and respectful maternal care during labour delivery services is limited. Therefore, this study aimed to assess compassionate and respectful maternity care, and its predictors, among those who gave birth in health facilities in North Gondar.

Methods

An institution-based cross-sectional study was conducted from May to July 2020 in a public health facility in North Gondar, Ethiopia. Systematic random sampling was used to select 398 study participants. Data were collected from participants using a pretested structured questionnaire. Bivariate and multivariate logistic regression model analyses with 95% confidence intervals were carried out to identify predictors of compassionate and respectful maternity care.

Results

A total of 398 respondents participated in the study. The overall prevalence of compassionate, respectful maternal care was 52.5%. Having primary school level education (adjusted odds ratio: 1.96), having attended antenatal care (adjusted odds ratio: 2.92), labour lasting for less than 6 hours (adjusted odds ratio: 2.22), and the intention to give birth in a health facility (adjusted odds ratio: 3.06) were significant predictors of compassionate and respectful maternity care.

Conclusions

The prevalence of compassionate and respectful maternity care was low and violations of women's rights are an important barrier to women seeking to give birth in a health facility. Hence, to promote high-quality maternal health services, health professionals must practice women-friendly approaches to improve the relationship between health workers and mothers during their stay at health facilities. Enforcing respectful maternity care is vital to strengthen maternal services and improve the rate of institution-based birth.
W-weighted GDMP inverse for rectangular matrices
Authors: Kumar Amit , Shekhar Vaibhav , Mishra Debasisha
Published: October 2022

In this article, we introduce two new generalized inverses for rectangular matrices called $W$-weighted generalized-Drazin--Moore--Penrose (GDMP) and $W$-weighted generalized-Drazin-reflexive (GDR) inverses. The first generalized inverse can be seen as a generalization of the recently introduced GDMP inverse for a square matrix to a rectangular matrix. The second class of generalized inverse contains the class of the first generalized inverse. We then exploit their various properties and establish that the proposed generalized inverses coincide with different well-known generalized inverses under certain assumptions. We also obtain a representation of $W$-weighted GDMP inverse employing EP-core nilpotent decomposition. We define the dual of $W$-weighted GDMP inverse and obtain analogue results. Further, we discuss additive properties, reverse- and forward-order laws for GD, $W$-weighted GD, GDMP, and $W$-weighted GDMP generalized inverses.
Energy Efficient Pneumatics: Aspects of Control and Systems Theory
Authors: Müller Daniel , Haag Jonathan , Wickert Jennifer , Raisch Adrian , Hoffmann Kathrin , Schmidt Kevin , Sawodny Oliver
Published: October 2022

As the public call for increasing efforts in achieving the global climate protection goals intensifies, discussions about the efficient use of resources and energy are on the daily agenda. As many other areas, the industry has seen itself facing growing concerns about the long neglected environmental aspects. Since a large proportion of the energy in production is used by pneumatic drives, this survey paper exclusively focuses on pneumatics in handling and automation technology and presents the most common components, followed by multiple model-based strategies to increase energy efficiency in modern production plants.
First, single units are studied extensively and methods for design and energy efficient control are presented. Since in production lines pneumatic drives are generally operated in large networks, the second part focuses on energy efficient strategies at plant level. These include an optimized adjustment of the supply pressure, a cascaded air usage, and an automated adaptive control pattern. Care is taken to ensure that the considered approaches are applicable in today’s industrial plants, which is demonstrated by experiments in a production line. The experimental findings show the immense potential of the discussed measures in the form of compressed air savings of more than 60% compared to the industry standard.
A Method for the Camera-less Remote Surveillance on Hydraulically Actuated Heavy Equipment Using IoT Environment
Authors: Zhidchenko Victor , Handroos Heikki
Published: October 2022

The paper considers the proposed method for the camera-less remote surveillance on hydraulically actuated heavy equipment. The method uses the data about the pressure and position of hydraulic actuators as an input. These data are transmitted over the internet in the Internet of Things (IoT) environment to the IoT cloud computing platform. A simulation model consisting of hydraulic and multibody dynamics submodels composes the digital twin of the machine under surveillance. This digital twin is maintained and calculated in the cloud. It reproduces the movements of the machine and calculates the forces acting in it. Together with the GPS coordinates, these data provide the full information on the machine operation. As a result, the productivity of the machine can be estimated, the misuse can be detected, and the load history can be gathered in order to estimate the remaining life of the machine or to plan the maintenance activities. The influence of the sensor accuracy on the simulation results is evaluated. The experimental results are presented that verify the feasibility of the proposed method on the example case of hydraulic mobile crane.
A Study on Trajectory Control System of Hydraulic Excavators Based on Multi-Domain Physical Model*
Authors: Zhang Zhen , Zhang Jingming , Luo Nianning
Published: October 2022

Hydraulic excavators are complex mechatronics construction machinery with characteristics of multidiscipline intersection and multi-domain close coupling. To analyze the comprehensive property of its trajectory control system, a method of multi-system hybrid modeling and simulation based on MATLAB is proposed and described. In this paper, the multi-domain physical model of a medium-sized hydraulic excavator is established. The considered model is mainly comprised of four other subsystems: a machine system, a hydraulic system, a trajectory control system and a sensor system. Moreover, a fuzzy neural network (FNN) PID strategy is introduced to the trajectory control system to guarantee the accuracy of automatic operation. On the basis of the multi-domain physical model, typical simulation experiments for working patterns were performed to validate the performance of the FNNPID controller. Comparison results demonstrate that the precision and velocity response of the FNNPID controller is better than that of the PID with traditional algorithm. The tracking errors of the boom, the arm, the bucket and the swing are decreased by 3∘, 3.2∘, 5.5∘ and 7.5∘, respectively. Establishment of the multi-domain physical model offers technical means for optimization design and rapid modeling of the complex electromechanical system.
Parallel optimization of tridimensional deformation measurement based on correlation function constraints of a multi-camera network
Authors: Zhang Guiyang , Wei Liang , Zhang Bin , Zhou Xing , Huo Ju
Published: October 2022

This study primarily investigates the low accuracy and redundant time-consuming problem of speckle registration in the full-field deformation measurement of slender and biggish specimens. To solve these problems, a parallel optimization of the tridimensional deformation measurement method is proposed based on what we believe is a novel correlation function constraints of a multi-camera network. First, a neotype correlation function is built based on the joint constraint relationship among the multiple cameras, which is capable of accurately restricting the search for homologous points in image pairs to the epipolar line, instead of the entire image, while significantly narrowing the search space and accelerating the search. The multiple cameras are bundled as a whole, thus reducing the dimension of the Jacobian matrix and the normalized matrix to a certain extent. Subsequently, more speckle images can be calculated in one iteration. Furthermore, the decomposition of the derived correlation function and the scheme of the parallel algorithm are decomposed via the kernel function based on the GPU parallel mechanism of the compute unified device architecture source program, thus increasing the subpixel search speed of speckle matching and ensuring the calculation performance of the stereo deformation measurement method to reach a higher level. Lastly, the experimental results revealed that the proposed strategy could allow the calculation speed-up ratio of speckle sequence and stereo registration to reach 20.390 times and 17.873 times, respectively, while ensuring the out-of-plane displacement average measuring accuracy to be higher than 0.179 mm within the spatial range of [2 m, 2 m, 3 m]. As a result, the proposed approach has crucial applications in rapid and stable tridimensional deformation measurement.
Topological photonics by breaking the degeneracy of line node singularities in semimetal-like photonic crystals
Authors: Börm Steffen , Davoodi Fatemeh , Köhl Ralf , Talebi Nahid
Published: October 2022

Degeneracy is an omnipresent phenomenon in various physical systems, which has its roots in the preservation of geometrical symmetry. In electronic and photonic crystal systems, very often this degeneracy can be broken by virtue of strong interactions between photonic modes of the same energy, where the level repulsion and the hybridization between modes causes the emergence of photonic bandgaps. However, most often this phenomenon does not lead to a complete and inverted bandgap formation over the entire Brillouin zone. Here, by systematically breaking the symmetry of a two-dimensional square photonic crystal, we investigate the formation of Dirac points, line node singularities, and inverted bandgaps. The formation of this complete bandgap is due to the level repulsion between degenerate modes along the line nodes of a semimetal-like photonic crystal, over the entire Brillouin zone. Our numerical experiments are performed by a home-build numerical framework based on a multigrid finite element method. The developed numerical toolbox and our observations pave the way towards designing complete bandgap photonic crystals and exploring the role of symmetry on the optical behaviour of even more complicated orders in photonic crystal systems.
Sine-limiting microcell solar concentrators for space
Authors: Ruud Christian J. , Gordon Jeffrey M. , McCarthy Robert F. , Giebink Noel C.
Published: October 2022

Microcell concentrating photovoltaics (µCPV) have the potential to improve performance and reduce the cost of solar power in space. Here, we introduce an ultracompact V-cone tailored edge ray (V-TERC) concentrator, rooted in nonimaging optics, which enables operation near the sine limit. Relative to previous space µCPV implementations, this concentrator design enables an approximate four-fold increase in concentration ratio for a given acceptance angle and specific power. We validate the design through ray tracing simulations and construction of a proof-of-concept system that consists of a 650 × 650 µm2 triple-junction microcell bonded to a 3.1 mm-thick prototype V-TERC optic. In outdoor testing on a sunny day, the system achieves a power conversion efficiency of 30% at a geometric gain of 137× with a specific power of 90 W kg-1 and an acceptance angle of ±4.5°. This is a record combination for µCPV to date and represents an important step toward increasing efficiency and lowering the cost of solar power in space.
Single optical element to generate a meter-scale THz diffraction-free beam
Authors: Tu Siyu , Peng Jinyu , Yang Zhengang , Liu Jinsong , Wang Kejia
Published: October 2022

Diffraction-free electromagnetic beam propagates in free space without change in its two-dimensional transverse profile. Elongating diffraction-free length can benefit the practical application of this beam. Here, we demonstrate that a THz diffraction-free beam with meter-scale length can be achieved by using only one optical element. By circumscribing the line-shape of spherical harmonic function on a traditional axicon, such optical element is designed, and then can be fabricated by 3D-printing technique. Simulated, experimental, and theoretical results all show that the diffraction-free length of generated beam is over 1000 mm. Further analysis based on Fourier optics theory indicates that the spatial frequency of this beam has a comb distribution, which plays a key role during the beam generation process. Moreover, such distribution also demonstrates the beam generated by our invented optical element is not the Bessel beam, but a new diffraction-free beam. It is believed that this meter-scale THz diffraction-free beam can be useful in a non-contact and non-destructive THz imaging system for large objects.
Double exceptional points in grating coupled metal-insulator-metal heterostructure
Authors: Mai Jianming , Chen Yu , Li Guixin , Cheah Kok Wai
Published: October 2022

In this work we theoretically study the exceptional points and reflection spectra characteristics of a grating coupled metal-insulator-metal heterostructure, which is a non-Hermitian system. Our results show that by selecting suitable geometrical parameters with grating periodicity @150 nm, that satisfy zero reflection condition, double exceptional points appear in a mode bifurcation regime. Furthermore, the thickness of partition metal layer between two cavities plays an important role in controlling the reflection properties of the heterostructure. There is a clear mode splitting when the partition layer allows strong coupling between the two cavity modes. Conversely, in weak coupling regime the mode splitting becomes too close to be distinguished. Moreover, the vanishing of reflection leads to unidirectional reflectionless propagation, which is also known as unidirectional invisibility. With grating periodicity ≥400nm, the transmissions for forward and backward incident directions are no longer the same due to the generation of diffraction. High contrast ratio (≈1) between the two incident directions leads to asymmetric transmission. This work lays the basis for designing double exceptional points and asymmetric transmission in coupled non-Hermitian photonics system. The proposed heterostructure can be a good candidate for new generation optical communications, optical sensing, photo-detection, and nano-photonic devices.
Effect of sidewall roughness on the diffraction efficiency of EUV high aspect ratio freestanding transmission gratings
Authors: Wu Shan , Wang Jinshi , Fang Fengzhou
Published: October 2022

Manufacturing-induced sidewall roughness has a significant impact on the diffraction efficiency of extreme ultraviolet (EUV) gratings and masks, which could be evaluated by a Debye-Waller damping factor. The rough profile models of line structures are always parallel to the surface for the reflective elements. In this manuscript, a model of rough lines along the thickness direction is established, which cannot be ignored for high aspect ratio transmission gratings. Numerical calculations are carried out using both a rigorous model and a Fraunhofer approximation model. The two models agree with each other on the low-order transmission efficiencies, and the fitted Debye-Waller factor indicates a larger roughness value than that of the model due to the absorption of EUV irradiation for 90° sidewall angle. When the sidewall angle is smaller than 88°, an extra degree of freedom is introduced to the traditional Debye-Waller factor-based formula. The +1-order transmission efficiency and absorptivity with smooth and rough sidewalls are also analyzed, as well as the effect of incidence angle, wavelength and grating thickness.
Mueller matrix imaging with a spatially modulated polarization light source
Authors: Leng Yan , Huang Tongyu , Pei Haojie , Hu Zheng , Guo Bin , Liao Ran , Ma Hui
Published: October 2022

In this paper, we present a Mueller matrix imaging system consisting of a spatially modulated polarization light source (SMPL) and a dual division-of-focal-plane (DoFP) polarimeters as the PSA and 2D detector. The system does not contain moving parts such as a rotating stage, which leads to more robust and reliable operations for applications in hostile settings. By taking Muller matrix images at variable distances between the SMPL and the target, we examine in details errors due to different spatial distributions in angle and intensity of different polarized lights. A calibration method is proposed to reduce such errors introduced by SMPL. The performances of the new imaging technique and the calibration method are tested in Mueller matrix imaging of different samples.
Theoretical investigation of active listening behavior based on the echolocation of CF-FM bats
Authors: Hiraga Takahiro , Yamada Yasufumi , Kobayashi Ryo
Published: October 2022

Bats perceive the three-dimensional environment by emitting ultrasound pulses from their nose or mouth and receiving echoes through both ears. To determine the position of a target object, it is necessary to know the distance and direction of the target. Certain bat species that use a combined signal of long constant frequency and short frequency modulated ultrasounds synchronize their pinnae movement with pulse emission, and this behavior has been regarded as helpful for localizing the elevation angle of a reflective sound source. However, the significance of bats’ ear motions remains unclear. In this study, we construct a model of an active listening system including the motion of the ears, and conduct mathematical investigations to clarify the importance of ear motion in direction detection of the reflective sound source. In the simulations, direction detection under rigid ear movements with interaural level differences was mathematically investigated by assuming that bats accomplish direction detection using the amplitude modulation in the echoes caused by ear movements. In particular, the ear motion conditions required for direction detection are theoretically investigated through exhaustive simulations of the pseudo-motion of the ears, rather than simulations of the actual ear motions of bats. The theory suggests that only certain ear motions, namely three-axis rotation, allow for accurate and robust direction detection. Our theoretical analysis also strongly supports the behavior whereby bats move their pinnae in the antiphase mode. In addition, we suggest that simple shaped hearing directionality and well-selected uncomplicated ear motions are sufficient to achieve precise and robust direction detection. Our findings and mathematical approach have the potential to be used in the design of active sensing systems in various engineering fields.
Prioritizing interventions for preventing COVID-19 outbreaks in military basic training
Authors: España Guido , Perkins T. Alex , Pollett Simon D. , Smith Morgan E. , Moore Sean M. , Kwon Paul O. , Hall Tara L. , Beagle Milford H. , Murray Clinton K. , Hakre Shilpa , Peel Sheila A. , Modjarrad Kayvon , Scott Paul T.
Published: October 2022

Like other congregate living settings, military basic training has been subject to outbreaks of COVID-19. We sought to identify improved strategies for preventing outbreaks in this setting using an agent-based model of a hypothetical cohort of trainees on a U.S. Army post. Our analysis revealed unique aspects of basic training that require customized approaches to outbreak prevention, which draws attention to the possibility that customized approaches may be necessary in other settings, too. In particular, we showed that introductions by trainers and support staff may be a major vulnerability, given that those individuals remain at risk of community exposure throughout the training period. We also found that increased testing of trainees upon arrival could actually increase the risk of outbreaks, given the potential for false-positive test results to lead to susceptible individuals becoming infected in group isolation and seeding outbreaks in training units upon release. Until an effective transmission-blocking vaccine is adopted at high coverage by individuals involved with basic training, need will persist for non-pharmaceutical interventions to prevent outbreaks in military basic training. Ongoing uncertainties about virus variants and breakthrough infections necessitate continued vigilance in this setting, even as vaccination coverage increases.
Markov state modelling reveals heterogeneous drug-inhibition mechanism of Calmodulin
Authors: Westerlund Annie M. , Sridhar Akshay , Dahl Leo , Andersson Alma , Bodnar Anna-Yaroslava , Delemotte Lucie
Published: October 2022

Calmodulin (CaM) is a calcium sensor which binds and regulates a wide range of target-proteins. This implicitly enables the concentration of calcium to influence many downstream physiological responses, including muscle contraction, learning and depression. The antipsychotic drug trifluoperazine (TFP) is a known CaM inhibitor. By binding to various sites, TFP prevents CaM from associating to target-proteins. However, the molecular and state-dependent mechanisms behind CaM inhibition by drugs such as TFP are largely unknown. Here, we build a Markov state model (MSM) from adaptively sampled molecular dynamics simulations and reveal the structural and dynamical features behind the inhibitory mechanism of TFP-binding to the C-terminal domain of CaM. We specifically identify three major TFP binding-modes from the MSM macrostates, and distinguish their effect on CaM conformation by using a systematic analysis protocol based on biophysical descriptors and tools from machine learning. The results show that depending on the binding orientation, TFP effectively stabilizes features of the calcium-unbound CaM, either affecting the CaM hydrophobic binding pocket, the calcium binding sites or the secondary structure content in the bound domain. The conclusions drawn from this work may in the future serve to formulate a complete model of pharmacological modulation of CaM, which furthers our understanding of how these drugs affect signaling pathways as well as associated diseases.
Rule-based and stimulus-based cues bias auditory decisions via different computational and physiological mechanisms
Authors: Tardiff Nathan , Suriya-Arunroj Lalitta , Cohen Yale E. , Gold Joshua I.
Published: October 2022

Expectations, such as those arising from either learned rules or recent stimulus regularities, can bias subsequent auditory perception in diverse ways. However, it is not well understood if and how these diverse effects depend on the source of the expectations. Further, it is unknown whether different sources of bias use the same or different computational and physiological mechanisms. We examined how rule-based and stimulus-based expectations influenced behavior and pupil-linked arousal, a marker of certain forms of expectation-based processing, of human subjects performing an auditory frequency-discrimination task. Rule-based cues consistently biased choices and response times (RTs) toward the more-probable stimulus. In contrast, stimulus-based cues had a complex combination of effects, including choice and RT biases toward and away from the frequency of recently presented stimuli. These different behavioral patterns also had: 1) distinct computational signatures, including different modulations of key components of a novel form of a drift-diffusion decision model and 2) distinct physiological signatures, including substantial bias-dependent modulations of pupil size in response to rule-based but not stimulus-based cues. These results imply that different sources of expectations can modulate auditory processing via distinct mechanisms: one that uses arousal-linked, rule-based information and another that uses arousal-independent, stimulus-based information to bias the speed and accuracy of auditory perceptual decisions.
Understanding molecular mechanisms and predicting phenotypic effects of pathogenic tubulin mutations
Authors: Attard Thomas J. , Welburn Julie P. I. , Marsh Joseph A.
Published: October 2022

Cells rely heavily on microtubules for several processes, including cell division and molecular trafficking. Mutations in the different tubulin-α and -β proteins that comprise microtubules have been associated with various diseases and are often dominant, sporadic and congenital. While the earliest reported tubulin mutations affect neurodevelopment, mutations are also associated with other disorders such as bleeding disorders and infertility. We performed a systematic survey of tubulin mutations across all isotypes in order to improve our understanding of how they cause disease, and increase our ability to predict their phenotypic effects. Both protein structural analyses and computational variant effect predictors were very limited in their utility for differentiating between pathogenic and benign mutations. This was even worse for those genes associated with non-neurodevelopmental disorders. We selected tubulin-α and -β disease mutations that were most poorly predicted for experimental characterisation. These mutants co-localise to the mitotic spindle in HeLa cells, suggesting they may exert dominant-negative effects by altering microtubule properties. Our results show that tubulin mutations represent a blind spot for current computational approaches, being much more poorly predicted than mutations in most human disease genes. We suggest that this is likely due to their strong association with dominant-negative and gain-of-function mechanisms.
Functional analysis of a bitter gustatory receptor highly expressed in the larval maxillary galea of Helicoverpa armigera
Authors: Chen Yan , Wang Pei-Chao , Zhang Shuai-Shuai , Yang Jun , Li Guo-Cheng , Huang Ling-Qiao , Wang Chen-Zhu
Published: October 2022

Many plant secondary substances are feeding deterrents for insects and play a key role in the selection of host plants. The taste sensilla of phytophagous insects contain gustatory sensory neurons sensitive to deterrents but the molecular basis of deterrent chemoreception remains unknown. We investigated the function of Gr180, the most highly expressed bitter gustatory receptor in the maxillary galea ofHelicoverpa armigeralarvae. Functional analyses using theXenopusoocyte expression system and two-electrode voltage clamp revealed that the oocytes expressing Gr180 responded to coumarin. Tip recording results showed that the medial sensilla styloconica of the maxilla of fifth instar larvae exhibited electrophysiological responses to coumarin. Two-choice feeding bioassays confirmed that coumarin inhibited larval feeding. A homozygous mutant strain ofH.armigerawith truncated Gr180 proteins (Gr180−/−) was established using the CRISPR-Cas9 system. The responses of the medial sensilla styloconica inGr180−/−to coumarin were almost abolished, and the responses to sinigrin and strychnine were also significantly decreased. Knockout ofGr180alleviated the feeding deterrent effects of coumarin, sinigrin, and strychnine. Thus, we conclude that Gr180 is a receptor responding to coumarin,and also participates in sensing sinigrin and strychnine. These results enhance our understanding of the gustatory sensing mechanisms of phytophagous insects to deterrents.
Proteomic profiling of serum extracellular vesicles identifies diagnostic markers for echinococcosis
Authors: Guo Xiaola , Wang Shuai , Zhang Junmei , Li Rui , Zhang Yong’e , Wang Zhengrong , Kong Qingming , Cho William C. , Ju Xianghong , Shen Yujuan , Zhang Lingqiang , Fan Haining , Cao Jianping , Zheng Yadong
Published: October 2022

Echinococcosis is a parasitic disease caused by the metacestodes of Echinococcus spp. The disease has a long latent period and is largely underdiagnosed, partially because of the lack of effective early diagnostic approaches. Using liquid chromatography-mass spectrometry, we profiled the serum-derived extracellular vesicles (EVs) of E. multilocularis-infected mice and identified three parasite-origin proteins, thioredoxin peroxidase 1 (TPx-1), transitional endoplasmic reticulum ATPase (TER ATPase), and 14-3-3, being continuously released by the parasites into the sera during the infection via EVs. Using ELISA, both TPx-1 and TER ATPase were shown to have a good performance in diagnosis of experimental murine echinococcosis as early as 10 days post infection and of human echinococcosis compared with that of control. Moreover, TER ATPase and TPx-1 were further demonstrated to be suitable for evaluation of the prognosis of patients with treatment. The present study discovers the potential of TER ATPase and TPx-1 as promising diagnostic candidates for echinococcosis.
LFA-1/ ICAM-1 promotes NK cell cytotoxicity associated with the pathogenesis of ocular toxoplasmosis in murine model
Authors: Gao Nannan , Wang Chong , Yu Yiran , Xie Linding , Xing Yien , Zhang Yuan , Wang Yanling , Wu Jianjun , Cai Yihong
Published: October 2022

Ocular toxoplasmosis (OT) is one of the most common causes of posterior uveitis. However, the pathogenic mechanisms of OT have not been well elucidated. Here, we used C57BL/6 (B6) mice to establish OT by peroral infection with 20 cysts of the TgCtWh6 strain, and severe ocular damage was observed by histopathological analysis in the eyes of infected mice. RNA-sequencing results showed that infection with T. gondii increased the expression of the NK-mediated cytotoxicity gene pathway at Day 30 after ocular T. gondii infection. Both NK-cell and CD49a+ NK-cell subsets are increased in ocular tissues, and the expression levels of LFA-1 in NK cells and ICAM-1 in the OT murine model were upregulated upon infection. Furthermore, inhibition of the interaction between LFA-1 and ICAM-1 with lifitegrast, a novel small molecule integrin antagonist, inhibited the protein expression of LFA-1 and ICAM-1 in murine OT and NK cells, improved the pathology of murine OT and influenced the secretion of cytokines in the OT murine model. In conclusion, the interaction between LFA-1 and ICAM-1 plays a role in the early regulation of the CD49a+ NK-cell proportion in an OT murine model. LFA-1/ ICAM-1 may be a key molecule in the pathogenesis of OT, and may provide new insights for potential immunotherapy.
Health system opportunities and challenges for PrEP implementation in Kenya: A qualitative framework analysis
Authors: Atkins Kaitlyn , Musau Abednego , Mugambi Mary , Odhyambo Geoffrey , Tengah Soud Ali , Kamau Mercy , Kumau Ruth , Reed Jason , Were Daniel
Published: October 2022

Background

As pre-exposure prophylaxis (PrEP) scales up in sub-Saharan Africa, governments and implementers need to understand how to best manage national programs. Kenya’s national PrEP program offers an opportunity to review elements of program success within the health system and evaluate the utility of a national implementation framework. We explored health system considerations for PrEP implementation to understand how Kenya’s national PrEP implementation priorities align with those of PrEP service providers, peer educators, and program or county managers.

Methods

We conducted twelve key informant interviews (KII) and nine focus group discussions (FGDs) with PrEP program and county managers (n = 12), peer educators (n = 44), and PrEP service providers (n = 48). We recruited participants across a variety of cadres and experiences with PrEP programs. KIIs and FGDs focused on PrEP service delivery and program implementation. Data were collected by trained study staff, audio recorded, translated into English, and transcribed. We used framework analysis methods to systematically apply Kenya’s 2017 National PrEP Implementation Framework to the data and summarized findings according to the seven Implementation Framework domains.

Results

All respondents emphasized the important role of communication, coordination, training, and leadership in PrEP implementation. PrEP service providers and program and county managers highlighted the importance of efficient data collection and utilization, and improved resource allocation. Commodity security and research, while key elements of the PrEP Implementation Framework, were less commonly discussed, and research was less prioritized by respondents. Respondents highlighted the importance of coordinated PrEP service delivery across sites and programs to improve overall client experiences.

Conclusion

In the context of a nationally-scaled PrEP program, PrEP service providers, peer educators, and program and county managers value strong leadership, close coordination of services across sites, and expedient use of data to improve strategies and services. Kenya’s PrEP Implementation Framework aligns closely with the priorities of individuals involved in PrEP service delivery and management, and provides a comprehensive overview of health system considerations for effective implementation of a PrEP program at scale.
Aggressive antipyretics in central nervous system malaria: Study protocol of a randomized-controlled trial assessing antipyretic efficacy and parasite clearance effects (Malaria FEVER study)
Authors: Chilombe Moses B. , McDermott Michael P. , Seydel Karl B. , Mathews Manoj , Mwenechanya Musaku , Birbeck Gretchen L.
Published: October 2022

Background

Malaria remains a major public health challenge in Africa where annually, ~250,000 children with malaria experience a neurologic injury with subsequent neuro-disability. Evidence indicates that a higher temperature during the acute illness is a risk factor for post-infectious neurologic sequelae. As such, aggressive antipyretic therapy may be warranted among children with complicated malaria at substantial risk of brain injury. Previous clinical trials conducted primarily in children with uncomplicated malaria and using only a single antipyretic medication have shown limited benefits in terms of fever reduction; however, no studies to date have examined malaria fever management using dual therapies. In this clinical trial of aggressive antipyretic therapy, children hospitalized with central nervous system (CNS) malaria will be randomized to usual care (acetaminophen every 6 hours for a temperature ≥ 38.5°C) vs. prophylactic acetaminophen and ibuprofen every 6 hours for 72 hours.

Methods

In this double-blinded, placebo controlled, two-armed clinical trial, we will enroll 284 participants from three settings at Queen Elizabeth Central Hospital in Blantyre, Malawi; at the University Teaching Hospitals Children’s Hospital in Lusaka, Zambia and at Chipata Central Hospital, Chipata, Zambia. Parents or guardians must provide written informed consent. Eligible participants are 2–11 years with evidence of P. falciparum malaria infection by peripheral blood smear or rapid diagnostic test with CNS symptoms associated with malaria. Eligible children will receive treatment allocation randomization either to standard of care for fever management or to prophylactic, scheduled treatment every 6 hours for 72 hours with dual antipyretic therapies using acetaminophen and ibuprofen. Assignment to treatment groups will be with 1:1 allocation using blocked randomization. The primary outcome will be maximum temperature in the 72 hours after enrolment. Secondary outcomes include parasite clearance as determined by quantitative Histidine Rich Protein II and seizures through 72 hours after enrolment.

Discussion

This clinical trial seeks to challenge the practice paradigm of limited fever treatment based upon hyperpyrexia by evaluating the fever-reduction efficacy of more aggressive antipyretic using two antipyretics and prophylactic administration and will elucidate the impact of antipyretics on parasite clearance and acute symptomatic seizures. If aggressive antipyretic therapy is shown to safely reduce the maximum temperature, a clinical trial evaluating the neuroprotective effects of temperature reduction in CNS malaria is warranted.
An exploratory study on the handwritten allographic features of multi-ethnic population with different educational backgrounds
Authors: Gannetion Linthini , Wong Kong Yong , Lim Poh Ying , Chang Kah Haw , Abdullah Ahmad Fahmi Lim
Published: October 2022

Ethnicity, native and/or foreign language knowledge, as well as the learned writing systems potentially influence the development of an individual’s handwriting. The unique education system consisting of National schools, Chinese-medium vernacular schools, Tamil-medium vernacular schools, and Islamic religious schools in Malaysia may have established specific characteristic handwritten allographic features that deserve investigation within the intelligence context. This study was aimed to explore handwritten allographic features of handwriting samples from 120 subjects (30 writers from four different educational backgrounds mentioned above). Characteristic features which could be attributed to the study groups were statistically analyzed and identified. In this study, thirteen allographic features, including letters "A", "B", "D", "H", "p", "T", "t", "w", "X" and "x", were found to be discriminative. Such information could serve to indicate the primary education system undergone by a writer; enabling the comparison of different handwriting profiles and allowing characterization of writers to a specific group of people.
On the Monte Carlo weights in multiple criteria decision analysis
Authors: Mazurek Jiří , Strzałka Dominik
Published: October 2022

In multiple-criteria decision making/aiding/analysis (MCDM/MCDA) weights of criteria constitute a crucial input for finding an optimal solution (alternative). A large number of methods were proposed for criteria weights derivation including direct ranking, point allocation, pairwise comparisons, entropy method, standard deviation method, and so on. However, the problem of correct criteria weights setting persists, especially when the number of criteria is relatively high. The aim of this paper is to approach the problem of determining criteria weights from a different perspective: we examine what weights’ values have to be for a given alternative to be ranked the best. We consider a space of all feasible weights from which a large number of weights in the form ofn−tuples is drawn randomly via Monte Carlo method. Then, we use predefined dominance relations for comparison and ranking of alternatives, which are based on the set of generated cases. Further on, we provide the estimates for a sample size so the results could be considered robust enough. At last, but not least, we introduce the concept ofcentral weightsand the measure of its robustness (stability) as well as the concept of alternatives’multi-dominance, and show their application to a real-world problem of the selection of the best wind turbine.