bluuebunny/crossref_metadata_2025 huggingface dataset:
Propagation of intense electromagnetic pulse with a small conical phase shift induced by Axicon optics
Authors: Moon Jeong Tae , Bulanov Sergei V. , Sasorov Pavel , Hadjisolomou Prokopis
Published: March 2023

The conical phase shift induced by the axicon generates a non-diffracting Bessel beam. In this paper, we examine the propagation property of an electromagnetic wave focused by a thin lens and axicon waveplate combination, which induces a small amount of conical phase shift less than one wavelength. A general expression describing the focused field distribution has been derived under the paraxial approximation. The conical phase shift breaks the axial symmetry of intensity and shows a focal spot-shaping capability by controlling the central intensity profile within a certain range near focus. The focal spot-shaping capability can be applied to form a concave or flattened intensity profile, which can be used to control the concavity of a double-sided relativistic flying mirror or to generate the spatially uniform and energetic laser-driven proton/ion beams for hadron therapy.
Efficient and accurate intensity diffraction tomography of multiple-scattering samples
Authors: Moser Simon , Jesacher Alexander , Ritsch-Marte Monika
Published: March 2023

Optical Diffraction Tomography (ODT) is a label-free method to quantitatively estimate the 3D refractive index (RI) distributions of microscopic samples. Recently, significant efforts were directed towards methods to model multiple-scattering objects. The fidelity of reconstructions rely on accurately modelling light-matter interactions, but the efficient simulation of light propagation through high-RI structures over a large range of illumination angles is still challenging. Here we present a solution dealing with these problems, proposing a method that allows one to efficiently model the tomographic image formation for strongly scattering objects illuminated over a wide range of angles. Instead of propagating tilted plane waves we apply rotations on the illuminated object and optical field and formulate a new and robust multi-slice model suitable for high-RI contrast structures. We test reconstructions made by our approach against simulations and experiments, using rigorous solutions to Maxwell’s equations as ground truth. We find the proposed method to produce reconstructions of higher fidelity compared to conventional multi-slice methods, especially for the challenging case of strongly scattering samples where conventional reconstruction methods fail.
Mimicking non-ideal instrument behavior for hologram processing using neural style translation
Authors: Schreck John S. , Hayman Matthew , Gantos Gabrielle , Bansemer Aaron , Gagne David John
Published: March 2023

Holographic cloud probes provide unprecedented information on cloud particle density, size and position. Each laser shot captures particles within a large volume, where images can be computationally refocused to determine particle size and location. However, processing these holograms with standard methods or machine learning (ML) models requires considerable computational resources, time and occasional human intervention. ML models are trained on simulated holograms obtained from the physical model of the probe since real holograms have no absolute truth labels. Using another processing method to produce labels would be subject to errors that the ML model would subsequently inherit. Models perform well on real holograms only when image corruption is performed on the simulated images during training, thereby mimicking non-ideal conditions in the actual probe. Optimizing image corruption requires a cumbersome manual labeling effort. Here we demonstrate the application of the neural style translation approach to the simulated holograms. With a pre-trained convolutional neural network, the simulated holograms are “stylized” to resemble the real ones obtained from the probe, while at the same time preserving the simulated image “content” (e.g. the particle locations and sizes). With an ML model trained to predict particle locations and shapes on the stylized data sets, we observed comparable performance on both simulated and real holograms, obviating the need to perform manual labeling. The described approach is not specific to holograms and could be applied in other domains for capturing noise and imperfections in observational instruments to make simulated data more like real world observations.
Dispersion-boosting wideband electromagnetic transparency under extreme angles for TE-polarized waves
Authors: Li Tiefu , Chu Zuntian , Han Yajuan , Yan Mingbao , Li Yongfeng , Qu Shaobo , Wang Jiafu , Feng Cunqian , Li Lei
Published: March 2023

Half-wave wall is the most common method of achieving electromagnetic (EM) transparency. Transmission windows can be formed when reflected waves are out of phase. Due to the interference mechanism, these windows are dependent on the frequency and incident angle of EM waves, leading to limited bandwidth, especially under extreme angles. In this letter, we propose to extend the bandwidth of the transmission window under extreme angles by utilizing dispersion. To this end, long metallic wires are embedded into the half-wave wall matrix, without increasing the physical thickness. Due to the plasma-like behavior of metallic wires under TE-polarization, the effective permittivity of the half-wave wall, rather than keeping constant, increases with frequency nonlinearly. Such a dispersion will boost wideband transparency in two aspects. On one hand, an additional transmission window will be generated where the effective permittivity equals that of the air; on the other hand, the 1st- and 2nd-order half-wave windows will be made quite closer. By tailoring the dispersion, the three windows can be merged to enable wideband transparency under extreme incident angles. A proof-of-principle prototype was designed, fabricated, and measured to verify this strategy. Both simulated and measured results show that the prototype can operate in the whole Ku-band under incident angle [70°, 85°] for TE-polarized waves. This work provides an effective method of achieving wideband EM transparency under extreme angles and may find applications in radar, communications, and others.
Photoacoustic remote sensing elastography
Authors: Yuan Yanchi , Wen Xue , Yuan Bo , Xin Haishu , Fang Bingyan , Yang Sihua , Xiong Kedi
Published: March 2023

The mechanical properties of organisms are important indicators for clinical disputes and disease monitoring, yet most existing elastography techniques are based on contact measurements, which are limited in many application scenarios. Photoacoustic remote sensing elastography (PARSE) is the first, to the best of our knowledge, elastography modality based on acoustic pressure monitoring, where elastic contrast information is obtained by using an all-optical non-contact and non-coherent intensity monitoring method through the time-response properties of laser-induced photoacoustic pressure. To validate PARSE, sections of different elastic organs were measured and this modality was applied to differentiate between bronchial cartilage and soft tissue to confirm the validity of the elasticity evaluation. PARSE, through a mathematical derivation process, has a 9.5-times greater distinction detection capability than photoacoustic remote sensing (PARS) imaging in stained bronchial sections, expands the scope of conventional PARS imaging, and has potential to become an important complementary imaging modality.
Computer holography using deep neural network with Fourier basis
Authors: Zhu Runze , Chen Lizhi , Zhang Hao
Published: March 2023

The use of a deep neural network is a promising technique for rapid hologram generation, where a suitable training dataset is vital for the reconstruct quality as well as the generalization of the model. In this Letter, we propose a deep neural network for phase hologram generation with a physics-informed training strategy based on Fourier basis functions, leading to orthonormal representations of the spatial signals. The spatial frequency characteristics of the reconstructed diffraction fields can be regulated by recombining the Fourier basis functions in the frequency domain. Numerical and optical results demonstrate that the proposed method can effectively improve the generalization of the model with high-quality reconstructions.
Diffraction-limited hyperspectral mid-infrared micro-ellipsometry
Authors: Ebner Alexander , Brunner Markus , Hingerl Kurt , Brandstetter Markus
Published: March 2023

The recent introduction of quantum cascade lasers (QCL) in infrared spectroscopic ellipsometry led to decisive improvements in measurement times and signal-to-noise ratios of this powerful analytical method. In this contribution, we present another significant enhancement leading to the first, to the best of our knowledge, diffraction-limited micro-ellisometry setup in the mid-infrared spectral range with a spatial resolution better than 13.3 µm. The fast spectral tunability of the QCL combined with phase-modulated polarization enabled simultaneous acquisition of broadband (900 cm−1–1204 cm−1) high-resolution (1 cm−1) hyperspectral Ψ, Δ-cubes in a scanning approach in reasonable time scales. The spatial resolution of the QCL micro-ellipsometer was experimentally characterized by the knife-edge method and measurements of a resolution test target. Furthermore, the hyperspectral ellipsometric investigation of a polymer multilayer cross section and the portrait window of a 200-euro bank note demonstrate the capabilities of diffraction-limited QCL micro-ellipsometry.
Spatial–spectral mapping to prepare frequency entangled qudits
Authors: Yang Zi-Xiang , Zeng Zi-Qi , Tian Ying , Wang Shun , Shimizu Ryosuke , Wu Hao-Yu , Liu Shilong , Jin Rui-Bo
Published: March 2023

Entangled qudits, the high-dimensional entangled states, play an important role in the study of quantum information. How to prepare entangled qudits in an efficient and easy-to-operate manner is still a challenge in quantum technology. Here, we demonstrate a method to engineer frequency entangled qudits in a spontaneous parametric downconversion process. The proposal employs an angle-dependent phase-matching condition in a nonlinear crystal, which forms a classical-quantum mapping between the spatial (pump) and spectral (biphotons) degrees of freedom. In particular, the pump profile is separated into several bins in the spatial domain, and thus shapes the down-converted biphotons into discrete frequency modes in the joint spectral space. Our approach provides a feasible and efficient method to prepare a high-dimensional frequency entangled state. As an experimental demonstration, we generate a three-dimensional entangled state by using a homemade variable slit mask.
Online polarization error suppressed optical vector analyzer based on Bayesian optimization
Authors: Huang Mingyang , Yu Zhangjun , Li Peijiong , Yang Jun , Wen Kunhua , Xu Pengbai , Wang Yuncai , Qin Yuwen
Published: March 2023

An optical vector analyzer (OVA) based on orthogonal polarization interrogation and polarization diversity detection is widely used to measure an optical device’s loss, delay, or polarization-dependent features. Polarization misalignment is the OVA’s primary error source. Conventional offline polarization alignment using a calibrator greatly reduces the measurement reliability and efficiency. In this Letter, we propose an online polarization error suppression method using Bayesian optimization. Our measurement results are verified by a commercial OVA instrument that uses the offline alignment method. The OVA featuring online error suppression will be widely used in the production of optical devices, not just in the laboratory.
Implementation and analysis of 32 channel CSRZ DWDM
system at narrow channel spacing
Authors: Dhadhal Dharmendra , Thummar Ruturaj , Mishra Vivekanand
Published: March 2023

In this work, we use CSRZ modulation at 32 x 40 Gbps DWDM long-haul communication system
under the effect of non-linearities using the dispersion compensation technique. The proposed system performance
is measured at 30 GHz, 40 GHz, and 50 GHz channel spacing in terms of BER, Q-factor, and eye-diagram for the
varied launched laser power ranging from −5 dBm to 10 dBm of CW laser array and 6000km transmission
distances. We use three EDFA amplifiers for signal amplification to boost signal power. By optimizing the system
parameters, we use pre and post-Gaussian filters at the transmission distance of 6000 km is achieved for a BER
value of 1.4306E-010 with a corresponding Q-factor value of 6.30611 at 5 dBm input power at 30GHz channel
spacing and without the Gaussian filter, we achieve Q factor is 4.18952 and BER is 1.35038E-05 at -5 dBm power
level at 50GHz channel spacing.
Inhibition of RANKL Expression in Osteocyte-like Differentiated Tumor Cells in Giant Cell Tumor of Bone After Denosumab Treatment
Authors: Noguchi Takashi , Sakamoto Akio , Murotani Yoshiki , Murata Koichi , Hirata Masahiro , Yamada Yosuke , Toguchida Junya , Matsuda Shuichi
Published: March 2023

Giant cell tumors of bone (GCTBs) are locally aggressive tumors with the histological features of giant cells and stromal cells. Denosumab is a human monoclonal antibody that binds to the cytokine receptor activator of nuclear factor–kappa B ligand (RANKL). RANKL inhibition blocks tumor-induced osteoclastogenesis, and survival, and is used to treat unresectable GCTBs. Denosumab treatment induces osteogenic differentiation of GCTB cells. In this study, the expression of RANKL, special AT-rich sequence-binding protein 2 (SATB2, a marker of osteoblast differentiation), and sclerostin/SOST (a marker of mature osteocytes) was analyzed before and after treatment with denosumab in six cases of GCTB. Denosumab therapy was administered a mean of five times over a mean 93.5-day period. Before denosumab treatment, RANKL expression was observed in one of six cases. After denosumab therapy, spindle-like cells devoid of giant cell aggregation were RANKL-positive in four of six cases. Bone matrix–embedded osteocyte markers were observed, although RANKL was not expressed. Osteocyte-like cells were confirmed to have mutations, as identified using mutation-specific antibodies. Our study results suggest that treatment of GCTBs with denosumab results in osteoblast–osteocyte differentiation. Denosumab played a role in the suppression of tumor activity via inhibition of the RANK–RANKL pathway, which triggers osteoclast precursors to differentiate into osteoclasts.
A Bayesian approach to incorporate structural data into the mapping of genotype to antigenic phenotype of influenza A(H3N2) viruses
Authors: Harvey William T. , Davies Vinny , Daniels Rodney S. , Whittaker Lynne , Gregory Victoria , Hay Alan J. , Husmeier Dirk , McCauley John W. , Reeve Richard
Published: March 2023

Surface antigens of pathogens are commonly targeted by vaccine-elicited antibodies but antigenic variability, notably in RNA viruses such as influenza, HIV and SARS-CoV-2, pose challenges for control by vaccination. For example, influenza A(H3N2) entered the human population in 1968 causing a pandemic and has since been monitored, along with other seasonal influenza viruses, for the emergence of antigenic drift variants through intensive global surveillance and laboratory characterisation. Statistical models of the relationship between genetic differences among viruses and their antigenic similarity provide useful information to inform vaccine development, though accurate identification of causative mutations is complicated by highly correlated genetic signals that arise due to the evolutionary process. Here, using a sparse hierarchical Bayesian analogue of an experimentally validated model for integrating genetic and antigenic data, we identify the genetic changes in influenza A(H3N2) virus that underpin antigenic drift. We show that incorporating protein structural data into variable selection helps resolve ambiguities arising due to correlated signals, with the proportion of variables representing haemagglutinin positions decisively included, or excluded, increased from 59.8% to 72.4%. The accuracy of variable selection judged by proximity to experimentally determined antigenic sites was improved simultaneously. Structure-guided variable selection thus improves confidence in the identification of genetic explanations of antigenic variation and we also show that prioritising the identification of causative mutations is not detrimental to the predictive capability of the analysis. Indeed, incorporating structural information into variable selection resulted in a model that could more accurately predict antigenic assay titres for phenotypically-uncharacterised virus from genetic sequence. Combined, these analyses have the potential to inform choices of reference viruses, the targeting of laboratory assays, and predictions of the evolutionary success of different genotypes, and can therefore be used to inform vaccine selection processes.
Robust deep learning object recognition models rely on low frequency information in natural images
Authors: Li Zhe , Ortega Caro Josue , Rusak Evgenia , Brendel Wieland , Bethge Matthias , Anselmi Fabio , Patel Ankit B. , Tolias Andreas S. , Pitkow Xaq
Published: March 2023

Machine learning models have difficulty generalizing to data outside of the distribution they were trained on. In particular, vision models are usually vulnerable to adversarial attacks or common corruptions, to which the human visual system is robust. Recent studies have found that regularizing machine learning models to favor brain-like representations can improve model robustness, but it is unclear why. We hypothesize that the increased model robustness is partly due to the low spatial frequency preference inherited from the neural representation. We tested this simple hypothesis with several frequency-oriented analyses, including the design and use of hybrid images to probe model frequency sensitivity directly. We also examined many other publicly available robust models that were trained on adversarial images or with data augmentation, and found that all these robust models showed a greater preference to low spatial frequency information. We show that preprocessing by blurring can serve as a defense mechanism against both adversarial attacks and common corruptions, further confirming our hypothesis and demonstrating the utility of low spatial frequency information in robust object recognition.
The effect of non-linear signal in classification problems using gene expression
Authors: Heil Benjamin J. , Crawford Jake , Greene Casey S.
Published: March 2023

Those building predictive models from transcriptomic data are faced with two conflicting perspectives. The first, based on the inherent high dimensionality of biological systems, supposes that complex non-linear models such as neural networks will better match complex biological systems. The second, imagining that complex systems will still be well predicted by simple dividing lines prefers linear models that are easier to interpret. We compare multi-layer neural networks and logistic regression across multiple prediction tasks on GTEx and Recount3 datasets and find evidence in favor of both possibilities. We verified the presence of non-linear signal when predicting tissue and metadata sex labels from expression data by removing the predictive linear signal with Limma, and showed the removal ablated the performance of linear methods but not non-linear ones. However, we also found that the presence of non-linear signal was not necessarily sufficient for neural networks to outperform logistic regression. Our results demonstrate that while multi-layer neural networks may be useful for making predictions from gene expression data, including a linear baseline model is critical because while biological systems are high-dimensional, effective dividing lines for predictive models may not be.
An associative memory Hamiltonian model for DNA and nucleosomes
Authors: Lu Weiqi , Onuchic José N. , Di Pierro Michele
Published: March 2023

A model for DNA and nucleosomes is introduced with the goal of studying chromosomes from a single base level all the way to higher-order chromatin structures. This model, dubbed the Widely Editable Chromatin Model (WEChroM), reproduces the complex mechanics of the double helix including its bending persistence length and twisting persistence length, and the temperature dependence of the former. The WEChroM Hamiltonian is composed of chain connectivity, steric interactions, and associative memory terms representing all remaining interactions leading to the structure, dynamics, and mechanical characteristics of the B-DNA. Several applications of this model are discussed to demonstrate its applicability. WEChroM is used to investigate the behavior of circular DNA in the presence of positive and negative supercoiling. We show that it recapitulates the formation of plectonemes and of structural defects that relax mechanical stress. The model spontaneously manifests an asymmetric behavior with respect to positive or negative supercoiling, similar to what was previously observed in experiments. Additionally, we show that the associative memory Hamiltonian is also capable of reproducing the free energy of partial DNA unwrapping from nucleosomes. WEChroM is designed to emulate the continuously variable mechanical properties of the 10nm fiber and, by virtue of its simplicity, is ready to be scaled up to molecular systems large enough to investigate the structural ensembles of genes. WEChroM is implemented in the OpenMM simulation toolkits and is freely available for public use.
Tuberculosis severity associates with variants and eQTLs related to vascular biology and infection-induced inflammation
Authors: McHenry Michael L. , Simmons Jason , Hong Hyejeong , Malone LaShaunda L. , Mayanja-Kizza Harriet , Bush William S. , Boom W. Henry , Hawn Thomas R. , Williams Scott M. , Stein Catherine M.
Published: March 2023

Background

Tuberculosis (TB) remains a major public health problem globally, even compared to COVID-19. Genome-wide studies have failed to discover genes that explain a large proportion of genetic risk for adult pulmonary TB, and even fewer have examined genetic factors underlying TB severity, an intermediate trait impacting disease experience, quality of life, and risk of mortality. No prior severity analyses used a genome-wide approach.

Methods and findings

As part of our ongoing household contact study in Kampala, Uganda, we conducted a genome-wide association study (GWAS) of TB severity measured by TBScore, in two independent cohorts of culture-confirmed adult TB cases (n = 149 and n = 179). We identified 3 SNPs (P<1.0 x 10–7) including one on chromosome 5, rs1848553, that was GWAS significant (meta-analysis p = 2.97x10-8). All three SNPs are in introns of RGS7BP and have effect sizes corresponding to clinically meaningful reductions in disease severity. RGS7BP is highly expressed in blood vessels and plays a role in infectious disease pathogenesis. Other genes with suggestive associations defined gene sets involved in platelet homeostasis and transport of organic anions. To explore functional implications of the TB severity-associated variants, we conducted eQTL analyses using expression data from Mtb-stimulated monocyte-derived macrophages. A single variant (rs2976562) associated with monocyte SLA expression (p = 0.03) and subsequent analyses indicated that SLA downregulation following MTB stimulation associated with increased TB severity. Src Like Adaptor (SLAP-1), encoded by SLA, is highly expressed in immune cells and negatively regulates T cell receptor signaling, providing a potential mechanistic link to TB severity.

Conclusions

These analyses reveal new insights into the genetics of TB severity with regulation of platelet homeostasis and vascular biology being central to consequences for active TB patients. This analysis also reveals genes that regulate inflammation can lead to differences in severity. Our findings provide an important step in improving TB patient outcomes.
Integration of cooperative and opposing molecular programs drives learning-associated behavioral plasticity
Authors: Nelson Jessica C. , Shoenhard Hannah , Granato Michael
Published: March 2023

Habituation is a foundational learning process critical for animals to adapt their behavior to changes in their sensory environment. Although habituation is considered a simple form of learning, the identification of a multitude of molecular pathways including several neurotransmitter systems that regulate this process suggests an unexpected level of complexity. How the vertebrate brain integrates these various pathways to accomplish habituation learning, whether they act independently or intersect with one another, and whether they act via divergent or overlapping neural circuits has remained unclear. To address these questions, we combined pharmacogenetic pathway analysis with unbiased whole-brain activity mapping using the larval zebrafish. Based on our findings, we propose five distinct molecular modules for the regulation of habituation learning and identify a set of molecularly defined brain regions associated with four of the five modules. Moreover, we find that in module 1 the palmitoyltransferase Hip14 cooperates with dopamine and NMDA signaling to drive habituation, while in module 3 the adaptor protein complex subunit Ap2s1 drives habituation by antagonizing dopamine signaling, revealing two distinct and opposing roles for dopaminergic neuromodulation in the regulation of behavioral plasticity. Combined, our results define a core set of distinct modules that we propose act in concert to regulate habituation-associated plasticity, and provide compelling evidence that even seemingly simple learning behaviors in a compact vertebrate brain are regulated by a complex and overlapping set of molecular mechanisms.
The duplicated P450s CYP6P9a/b drive carbamates and pyrethroids cross-resistance in the major African malaria vector Anopheles funestus
Authors: Mugenzi Leon M. J. , A. Tekoh Theofelix , S. Ibrahim Sulaiman , Muhammad Abdullahi , Kouamo Mersimine , Wondji Murielle J. , Irving Helen , Hearn Jack , Wondji Charles S.
Published: March 2023

Cross-resistance to insecticides in multiple resistant malaria vectors is hampering resistance management. Understanding its underlying molecular basis is critical to implementation of suitable insecticide-based interventions. Here, we established that the tandemly duplicated cytochrome P450s, CYP6P9a/b are driving carbamate and pyrethroid cross-resistance in Southern African populations of the major malaria vector Anopheles funestus.

Transcriptome sequencing revealed that cytochrome P450s are the most over-expressed genes in bendiocarb and permethrin-resistant An. funestus. The CYP6P9a and CYP6P9b genes are overexpressed in resistant An. funestus from Southern Africa (Malawi) versus susceptible An. funestus (Fold change (FC) is 53.4 and 17 respectively), while the CYP6P4a and CYP6P4b genes are overexpressed in resistant An. funestus in Ghana, West Africa, (FC is 41.1 and 17.2 respectively). Other up-regulated genes in resistant An. funestus include several additional cytochrome P450s (e.g. CYP9J5, CYP6P2, CYP6P5), glutathione-S transferases, ATP-binding cassette transporters, digestive enzymes, microRNA and transcription factors (FC<7). Targeted enrichment sequencing strongly linked a known major pyrethroid resistance locus (rp1) to carbamate resistance centering around CYP6P9a/b. In bendiocarb resistant An. funestus, this locus exhibits a reduced nucleotide diversity, significant p-values when comparing allele frequencies, and the most non-synonymous substitutions. Recombinant enzyme metabolism assays showed that both CYP6P9a/b metabolize carbamates. Transgenic expression of CYP6P9a/b in Drosophila melanogaster revealed that flies expressing both genes were significantly more resistant to carbamates than controls. Furthermore, a strong correlation was observed between carbamate resistance and CYP6P9a genotypes with homozygote resistant An. funestus (CYP6P9a and the 6.5kb enhancer structural variant) exhibiting a greater ability to withstand bendiocarb/propoxur exposure than homozygote CYP6P9a_susceptible (e.g Odds ratio = 20.8, P<0.0001 for bendiocarb) and heterozygotes (OR = 9.7, P<0.0001). Double homozygote resistant genotype (RR/RR) were even more able to survive than any other genotype combination showing an additive effect.

This study highlights the risk that pyrethroid resistance escalation poses to the efficacy of other classes of insecticides. Available metabolic resistance DNA-based diagnostic assays should be used by control programs to monitor cross-resistance between insecticides before implementing new interventions.
Rhometa: Population recombination rate estimation from metagenomic read datasets
Authors: Krishnan Sidaswar , DeMaere Matthew Z. , Beck Dominik , Ostrowski Martin , Seymour Justin R. , Darling Aaron E.
Published: March 2023

Prokaryotic evolution is influenced by the exchange of genetic information between species through a process referred to as recombination. The rate of recombination is a useful measure for the adaptive capacity of a prokaryotic population. We introduce Rhometa (https://github.com/sid-krish/Rhometa), a new software package to determine recombination rates from shotgun sequencing reads of metagenomes. It extends the composite likelihood approach for population recombination rate estimation and enables the analysis of modern short-read datasets. We evaluated Rhometa over a broad range of sequencing depths and complexities, using simulated and real experimental short-read data aligned to external reference genomes. Rhometa offers a comprehensive solution for determining population recombination rates from contemporary metagenomic read datasets. Rhometa extends the capabilities of conventional sequence-based composite likelihood population recombination rate estimators to include modern aligned metagenomic read datasets with diverse sequencing depths, thereby enabling the effective application of these techniques and their high accuracy rates to the field of metagenomics. Using simulated datasets, we show that our method performs well, with its accuracy improving with increasing numbers of genomes. Rhometa was validated on a real S. pneumoniae transformation experiment, where we show that it obtains plausible estimates of the rate of recombination. Finally, the program was also run on ocean surface water metagenomic datasets, through which we demonstrate that the program works on uncultured metagenomic datasets.
Treatment with benznidazole and pentoxifylline regulates microRNA transcriptomic profile in a murine model of Chagas chronic cardiomyopathy
Authors: Silva Grijó Farani Priscila , Iandra da Silva Ferreira Beatriz , Begum Khodeza , Vilar-Pereira Glaucia , Pereira Isabela Resende , Fernández-Figueroa Edith A. , Cardenas-Ovando Roberto Alejandro , Almeida Igor C. , Roy Sourav , Lannes-Vieira Joseli , Moreira Otacilio Cruz
Published: March 2023

Chronic Chagas cardiomyopathy (CCC) is one of the leading causes of morbidity and mortality due to cardiovascular disorders in endemic areas of Chagas disease (CD), a neglected tropical illness caused by the protozoan parasiteTrypanosoma cruzi. CCC is characterized by parasite persistence and inflammatory response in the heart tissue, which occur parallel to microRNA (miRNA) alterations. Here, we investigated the miRNA transcriptome profiling in the cardiac tissue of chronicallyT.cruzi-infected mice treated with a suboptimal dose of benznidazole (Bz), the immunomodulator pentoxifylline alone (PTX), or the combination of both (Bz+PTX), following the CCC onset. At 150 days post-infection, Bz, PTX, and Bz+PTX treatment regimens improved electrocardiographic alterations, reducing the percentage of mice afflicted by sinus arrhythmia and second-degree atrioventricular block (AVB2) when compared with the vehicle-treated animals. miRNA Transcriptome profiling revealed considerable changes in the differential expression of miRNAs in the Bz and Bz+PTX treatment groups compared with the control (infected, vehicle-treated) group. The latter showed pathways related to organismal abnormalities, cellular development, skeletal muscle development, cardiac enlargement, and fibrosis, likely associated with CCC. Bz-Treated mice exhibited 68 differentially expressed miRNAs related to signaling pathways like cell cycle, cell death and survival, tissue morphology, and connective tissue function. Finally, the Bz+PTX-treated group revealed 58 differentially expressed miRNAs associated with key signaling pathways related to cellular growth and proliferation, tissue development, cardiac fibrosis, damage, and necrosis/cell death. TheT.cruzi-induced upregulation of miR-146b-5p, previously shown in acutely infected mice andin vitro T.cruzi-infected cardiomyocytes, was reversed upon Bz and Bz+PTX treatment regimens when further experimentally validated. Our results further our understanding of molecular pathways related to CCC progression and evaluation of treatment response. Moreover, the differentially expressed miRNAs may serve as drug targets, associated molecular therapy, or biomarkers of treatment outcomes.
Effect of postural threat on motor control in people with and without low back pain
Authors: Wildenbeest Meta H. , Kiers Henri , Tuijt Matthijs , van Dieën Jaap H.
Published: March 2023

Introduction

Negative pain-related cognitions are associated with persistence of low-back pain (LBP), but the mechanism underlying this association is not well understood. We propose that negative pain-related cognitions determine how threatening a motor task will be perceived, which in turn will affect how lumbar movements are performed, possibly with negative long-term effects on pain.

Objective

To assess the effect of postural threat on lumbar movement patterns in people with and without LBP, and to investigate whether this effect is associated with task-specific pain-related cognitions.

Methods

30 back-healthy participants and 30 participants with LBP performed consecutive two trials of a seated repetitive reaching movement (45 times). During the first trial participants were threatened with mechanical perturbations, during the second trial participants were informed that the trial would be unperturbed. Movement patterns were characterized by temporal variability (CyclSD), local dynamic stability (LDE) and spatial variability (meanSD) of the relative lumbar Euler angles. Pain-related cognition was assessed with the task-specific ‘Expected Back Strain’-scale (EBS). A three-way mixed Manova was used to assess the effect of Threat, Group (LBP vs control) and EBS (above vs below median) on lumbar movement patterns.

Results

We found a main effect of threat on lumbar movement patterns. In the threat-condition, participants showed increased variability (MeanSDflexion-extension, p<0.000, η2 = 0.26; CyclSD, p = 0.003, η2 = 0.14) and decreased stability (LDE, p = 0.004, η2 = 0.14), indicating large effects of postural threat.

Conclusion

Postural threat increased variability and decreased stability of lumbar movements, regardless of group or EBS. These results suggest that perceived postural threat may underlie changes in motor behavior in patients with LBP. Since LBP is likely to impose such a threat, this could be a driver of changes in motor behavior in patients with LBP, as also supported by the higher spatial variability in the group with LBP and higher EBS in the reference condition.
Digital inclusive finance & the high-quality agricultural development: Prevalence of regional heterogeneity in rural China
Authors: Li Hanjin , Shi Yang , Zhang Jianxin , Zhang Zhenkun , Zhang Zhaosen , Gong Maogang
Published: March 2023

Developing digital inclusive finance is one of the most effective ways to alleviate financial exclusion in the agriculture sector. For empirical investigation, data from 30 provinces of Rural China is collected from the period 2011 to 2020. The study constructs five dimensions and 22 indicators in total to critically conduct the impact of digital inclusive finance on high-quality agricultural development. The level of agricultural development is measured by entropy weight TOPSIS, and the impact of digital inclusive finance on its high-quality development is empirically tested. The results show that digital inclusive finance has significantly improved the agricultural sector and, particularly, the Eastern region of China has the greatest impact. Three dimensions of digital inclusion finance have regional heterogeneity in terms of impact on agricultural development in Rural China. Data does not show the simple linear relationship between digital inclusion finance and agricultural development quality. The impact of the former on the latter is characterized by the double thresholds. The digital inclusive finance index is the weakest when it is lower than the first threshold that is 4.7704, and the impact of the second threshold that is 5.3186 on high-quality agricultural development is gradually enhanced. After crossing the second threshold, the impact of digital inclusive finance on high-quality agricultural development in Rural China is significantly enhanced. The development of digital inclusive finance should be strengthened in the Central and Western regions to compensate for regional financial imbalances and promote synergy in the high-quality development of agriculture across the country.
Health professionals’ perceptions on local production and bioequivalence study of generic medicines: A cross-sectional survey of physicians and pharmacy professionals in Addis Ababa, Ethiopia
Authors: Selam Muluken Nigatu , Mengstu Abrham Temesgen , Fentie Atalay Mulu , Gebretekle Gebremedhin Beedemariam , Ali Eskinder Eshetu , Belete Anteneh
Published: March 2023

Local production of generic medicines in developing countries has a critical role to meet public health needs by ensuring the availability of essential medicines and providing patients’ relief from the burden of unaffordable medical bills. Compliance with bioequivalence (BE) requirements increase the quality and competitiveness of generic drugs regardless of the source. In this regard, a regional BE center has been established in Addis Ababa, Ethiopia to serve the needs of Ethiopia and neighbouring countries. The present study aimed to assess the knowledge and perceptions of health professionals working in Addis Ababa regarding local production and BE studies of generic medicines. A cross-sectional survey was employed and physician participants working at public hospitals and pharmacists from various practice settings were selected using convenient sampling technique. Data was collected using self-administered structured questionnaire. Descriptive statistics was used to summarize the data and multinomial logistic regression analyses was used to assess predictors of health professionals’ perception towards the source of drugs. Statistically significant association was declared at p-value < 0.05. A total of 416 participants responded and 272 (65.4%) of them were male. Nearly half of the study participants (n = 194) preferred the imported products. Compared to physicians, participants with diploma (AOR = 0.40; 95%CI: 0.18–0.91, p = 0.028) and bachelor degree and above holders (AOR = 0.32; 95%CI: 0.15–0.68, p = 0.003) in pharmacy were more likely to prefer locally produced products. Participants who practiced in pharmaceutical industries (AOR = 0.40, 95%CI: 0.22–0.77, p = 0.006) preferred locally manufactured products as compared to those practicing in the hospital. While a majority (321, 77.2%) believed in the advantages of doing BE studies locally, only 106 (25.5%) recognized that local pharmaceutical manufacturers did not implement BE studies for their generic products and lack of enforcement by the national regulatory body was raised as a reason for not conducting BE studies by most of the participants (67.9%). The present study revealed a modest preference by physicians and pharmacy professionals towards locally produced products. Majority of participants supported the idea of doing BE studies locally. However, manufacturers and regulators should devise ways to increase health professionals’ confidence in local products. Strengthening local BE study capacity is also highly recommended.
Effects of an eastward shift in the Agulhas retroflection region on chlorophyll-a bloom on its south flank
Authors: Ding Xiaoqi , Shen Hao , Sun Jialong , Bai Linfei , Peng Lin , LÜ Haibin
Published: March 2023

As observed by remote sensing images in December 2013 and January 2014, chlorophyll-a (Chl-a) bloom occurred on the south side of the Agulhas Current (38°S-45°S). The dynamic mechanisms of Chl-a bloom were studied by satellite remote sensing data, reanalysis data and Argo data. The periodic shedding of the Agulhas ring led to a significant eastward shift of the Agulhas retroflection from December 2013 to January 2014, without the obstruction of flowing complex eddies and with increased current flow. Then, the horizontal transfer of Chl-a occurred along the south side of the Agulhas Current (38°S-45°S). Nitrate concentrations reached 10–15 μmol·L-1 on the south side of the Agulhas Current, where a deepened mixed layer and upwelling and the vertical transport of nutrients contributed to the Chl-a bloom. In addition, sufficient light and suitable precipitation provide good conditions for Chl-a bloom on the south side of the Agulhas Current.
Correlation between reading time and characteristics of eye fixations and progressive lens design
Authors: Concepcion-Grande Pablo , Chamorro Eva , Cleva Jose Miguel , Alonso Jose , Gómez-Pedrero Jose Antonio
Published: March 2023

Objective

The purpose of this study is to evaluate reading time and characteristics of fixations at different distances when looking through different areas of progressive power lenses (PPL) with different power distributions by means of eye-tracking technology.

Method

A wearable eye tracker system (Tobii-Pro Glasses 3) was used to record the pupil position of 28 PPL subjects when reading at near and distance vision while using 3 different PPL designs: a PPL optimized for distance vision (PPL-Distance), a PPL optimized for near vision (PPL-Near) and one of them balanced for a general use (PPL-Balance). Subjects were asked to read out loud a text displayed on a digital screen located at 5.25m and 0.37m when they were looking through the central and peripheral regions of each PPL. Reading time, total duration of fixations, and the number of fixations were analyzed for each reading condition and PPL. Statistical analysis was carried out using Statgraphics Centurion XVII.II Software.

Results

The analysis of eye movements at distance-reading vision showed a statistically significant lower reading time (p = 0.004) and lower total duration of fixations (p = 0.01) for PPL-Distance. At near-reading vision, PPL-Near provided statistically significant lower reading time (p<0.001), lower total duration of fixations (p = 0.02), and less fixation count(p<0.001) in comparison with PPL-Balance and PPL-Distance.

Conclusions

Reading time and fixations characteristics are affected by the power distribution of a PPL. A PPL design with a wider distance region provides better distance-reading performance while a PPL with a wider near area performs better at a near-reading task. The power distribution of PPLs influences the user performance at vision-based tasks. Thus, to provide the user with the best visual experience, PPL selection must consider user needs.
An evaluation of LLIN ownership, access, and use during the Magude project in southern Mozambique
Authors: Fernández Montoya Lucia , Alafo Celso , Martí-Soler Helena , Máquina Mara , Malheia Arlindo , Sacoor Charfudin , Abílio Ana Paula , Marrenjo Dulcisaria , Cuamba Nelson , Galatas Beatriz , Aide Pedro , Saúte Francisco , Paaijmans Krijn P.
Published: March 2023

The Magude Project assessed the feasibly of eliminating malaria in a low transmission setting in southern Mozambique using a package of interventions. This study measured the ownership, access and use of long-lasting insecticide treated nets (LLINs) and inequalities in these indicators across household wealth, size and population subgroups, to understand the protection that LLINs provided during the project. Data were obtained from various household surveys. At least 31% of the nets distributed during the 2014 and 2017 campaigns were lost during the first year post-distribution. Most nets (77.1%) present in the district were Olyset Nets. LLIN access never exceeded 76.3% and use varied seasonally between 40% and 76.4%. LLIN access limited LLIN use during the project, especially during the high transmission season. LLIN ownership, access and use were lower in harder-to-reach localities, in poorer and larger households. Children and women below 30 had poorer access to LLINs than the overall population. Net use was lowest among school-aged children and young adults, especially among young males, and highest in children under 5, pregnant women, in older adults and in households that received indoor residual spraying (IRS). This study revealed that LLIN mass-distribution campaigns alone are not sufficient to achieve the high level of net protection needed during elimination programs and that reviewing the LLIN allocation scheme, top-up distributions and/or community engagement campaigns is needed, also to reduce inequalities in populations’ access to LLINs.
IL-12p40 is essential but not sufficient for Francisella tularensis LVS clearance in chronically infected mice
Authors: Mittereder Lara R. , Swoboda Jonathan , De Pascalis Roberto , Elkins Karen L.
Published: March 2023

IL-12p40 plays an important role in F. tularensis Live Vaccine Strain (LVS) clearance that is independent of its functions as a part of the heterodimeric cytokines IL-12p70 or IL-23. In contrast to WT, p35, or p19 knockout (KO) mice, p40 KO mice infected with LVS develop a chronic infection that does not resolve. Here, we further evaluated the role of IL-12p40 in F. tularensis clearance. Despite reduced IFN-γ production, primed splenocytes from p40 KO and p35 KO mice appeared functionally similar to those from WT mice during in vitro co-culture assays of intramacrophage bacterial growth control. Gene expression analysis revealed a subset of genes that were upregulated in re-stimulated WT and p35 KO splenocytes, but not p40 KO splenocytes, and thus are candidates for involvement in F. tularensis clearance. To directly evaluate a potential mechanism for p40 in F. tularensis clearance, we reconstituted protein levels in LVS-infected p40 KO mice using either intermittent injections of p40 homodimer (p80) or treatment with a p40-producing lentivirus construct. Although both delivery strategies yielded readily detectable levels of p40 in sera and spleens, neither treatment had a measurable impact on LVS clearance by p40 KO mice. Taken together, these studies demonstrate that clearance of F. tularensis infection depends on p40, but p40 monomers and/or dimers alone are not sufficient.