Miracle-dz/UniFAR-FTUs huggingface dataset:
Optimization of phase-variation measurements in low-coherence methods: implications for OCE

Phase-resolved measurements found numerous applications in low-coherence methods, in particular in OCT-based compressional elastography, where phase-variation gradients are used for estimating strains produced by the OCT probe pressed onto the tissue. Conventionally, for the reference and deformed pixelated OCT scans, one performs comparison of phases taken from pixels with the same coordinates. This is reasonable in regions of sufficiently small sub-pixel displacements, for which the so-compared pixels contain the same scatterers. Furthermore, to avoid error-prone multiple phase unwrapping for reconstructing displacements, one have to ensure even smaller sub-wavelength displacements. This limits the allowable strains to less than ~10-4-10-3, although such weak phase gradients can be strongly corrupted by measurement noises. Here, we discuss how creation of an order of magnitude greater strains can be used for increasing the signal-to noise ratio in estimating phase gradients by obviating the phase-unwrapping procedures and reducing the influence of decorrelation noise for supra-pixel displacements. This optimized phase-variation measurement makes it possible to perform strain mapping in optical coherence elastography with exceptionally high tolerance to noises due to possibility of using significantly increased strains. We also discuss the effect of “frozen-phase zones” associated with displaced strong scatterers. This effect can result in appearance of artifacts in the form of false stiff inclusions in elastograms in the vicinity of bright scatterers in OCT scans. We present analytical arguments, numerical simulations and experimental examples illustrating the above-mentioned features of the “frozen-phase” effect and advantages of using the proposed optimized phase-variation measurement with pixel-scale displacement compensation in the compared OCT scans.
Upper solution bound of the CCARE and its application in multi-agent systems with time-delay in the state

Stability is important for control systems. In this paper, using the transformation of the matrix equations and some significant properties of the matrix inequality, we derived new upper solution bounds of the continuous coupled algebraic Riccati equation (CCARE). The new bounds are more precise than those proposed in some existing works on this topic numerically. Next, a condition for the stability of multi-agent systems with time-delay in the state is presented according to the upper solution bound of the CCARE. Finally, corresponding numerical examples are provided to illustrate the superior and effectiveness of the derived results.
Formalin fixation and paraffin embedding interfere with preservation of optical metabolic assessments based on endogenous NAD(P)H and FAD two photon excited fluorescence

Endogenous NAD(P)H and FAD two-photon excited fluorescence (TPEF) images provide functional metabolic information with high spatial resolution for a wide range of living specimens. Preservation of metabolic function optical metrics upon fixation would facilitate studies which assess the impact of metabolic changes in the context of numerous diseases. However, robust assessments of the impact of formalin fixation, paraffin embedding, and sectioning on the preservation of optical metabolic readouts are lacking. Here, we evaluate intensity and lifetime images at excitation/emission settings optimized for NAD(P)H and FAD TPEF detection from freshly excised murine oral epithelia and corresponding bulk and sectioned fixed tissues. We find that fixation impacts the overall intensity as well as the intensity fluctuations of the images acquired. Accordingly, the depth-dependent variations of the optical redox ratio (defined as FAD/(NAD(P)H + FAD)) across squamous epithelia are not preserved following fixation. This is consistent with significant changes in the 755 nm excited spectra, which reveal broadening upon fixation and additional distortions upon paraffin embedding and sectioning. Analysis of fluorescence lifetime images acquired for excitation/emission settings optimized for NAD(P)H TPEF detection indicate that fixation alters the long lifetime of the observed fluorescence and the long lifetime intensity fraction. These parameters as well as the short TPEF lifetime are significantly modified upon embedding and sectioning. Thus, our studies highlight that the autofluorescence products formed during formalin fixation, paraffin embedding and sectioning overlap highly with NAD(P)H and FAD emission and limit the potential to utilize such tissues to assess metabolic activity.
DNA binding redistributes activation domain ensemble and accessibility in pioneer factor Sox2

More than 1600 human transcription factors orchestrate the transcriptional machinery to control gene expression and cell fate. Their function is conveyed through intrinsically disordered regions (IDRs) containing activation or repression domains but lacking quantitative structural ensemble models prevents their mechanistic decoding. Here we integrate single-molecule FRET and NMR spectroscopy with molecular simulations showing that DNA binding can lead to complex changes in the IDR ensemble and accessibility. The C-terminal IDR of pioneer factor Sox2 is highly disordered but its conformational dynamics are guided by weak and dynamic charge interactions with the folded DNA binding domain. Both DNA and nucleosome binding induce major rearrangements in the IDR ensemble without affecting DNA binding affinity. Remarkably, interdomain interactions are redistributed in complex with DNA leading to variable exposure of two activation domains critical for transcription. Charged intramolecular interactions allowing for dynamic redistributions may be common in transcription factors and necessary for sensitive tuning of structural ensembles.
Linewidth Enhancement Factor in GaAs/AlGaAs Multi-Quantum-Well Lasers

The linewidth enhancement factor α in GaAs/AlGaAs multi-quantum-well (MQW) lasers has been determined from the spontaneous emission spectra below threshold. It is demonstrated that the value of α in MQW lasers is appreciably smaller than that in conventional double heterostructure (DH) lasers because of the enhanced carrier-density-derivative of the optical gain.
Inhibition of Notch activity by phosphorylation of CSL in response to parasitization in Drosophila

Notch signaling activity regulates hematopoiesis in Drosophila and vertebrates alike. Parasitoid wasp infestation of Drosophila larvae, however, requires a rapid downregulation of Notch activity to allow the formation of encapsulation-active blood cells. Here we show that the Drosophila CSL transcription factor Suppressor of Hairless [Su(H)] is phosphorylated at Serine 269 in response to parasitoid wasp infestation. As this phosphorylation interferes with the DNA-binding of Su(H), it reversibly inhibits Notch activity. Accordingly, phospho-deficient Su(H)S269A mutants are immune compromised. A screen for kinases involved in Su(H) phosphorylation identified Pkc53E, required for normal hematopoiesis as well as for parasitoid immune response. Genetic and molecular interactions support the specificity of the Su(H)-Pkc53E relationship. Moreover, phorbol ester treatment inhibits Su(H) activity in vivo and in human cell culture. We conclude that Pkc53E targets Su(H) during parasitic wasp infestation, inducing downregulation of Notch activity, thereby remodeling the blood cell population required for wasp egg encapsulation.
HSP90 inhibitor NVP-HSP990 alleviates rotavirus infection

Rotavirus (RV) infection is an important cause of hospitalization and even death of infants and young children, but conventional antiviral drugs such as nucleoside analogues as well as type I interferon are usually not included in treatment of RV diarrhea due to adverse side effects. Host heat shock protein 90 (HSP90) is commonly up-regulated and exploited by a series of viruses for successful infection including RV, rendering the possibility of small molecule HSP90 inhibitors as novel antiviral agents for control of RV infection. Here, we tested the effect of a novel HSP90 inhibitor NVP-HSP990 (HSP990), which possesses excellent oral bioavailability, on alleviating RV infection in vitro and in vivo. We found that HSP990 was low-cytotoxic and potently inhibited RV replication in MA104 and Caco-2 cells, though largely did not influence initial establishment of RV infection. Meanwhile, HSP990 also remarkably inhibited the activation of MAPK pathways induced by RV infection. HSP990 effectively alleviates RV diarrhea of BABL/c suckling mice, and remarkably inhibited RV replication as well as expressions of pro-inflammatory cytokines/chemokines in epithelial cells of intestinal mucosa. IMPORTANCE We revealed the novel HSP90 small molecule inhibitor HSP990 was a novel potent antiviral agent with low cytotoxity for the first time. HSP990 significantly inhibited RV replication in vitro and in vivo with low cytotoxicity and effectively alleviated RV diarrhea. These findings indicated that HSP990 could be a novel promising candidate of antiviral drug for RV infection.
The Janelia Atalanta plasmids provide a simple and efficient CRISPR/Cas9-mediated homology directed repair platform for Drosophila

Homology-directed repair (HDR) is a powerful tool for modifying genomes in precise ways to address many biological questions. Use of Clustered Regularly Interspersed Short Palindromic Repeats (CRISPR)-Cas9 induced targeted DNA double-strand breakage has substantially simplified use of homology-directed repair to introduce specific perturbations in Drosophila, but existing platforms for CRISPR-Cas9-mediated HDR in Drosophila involve multiple cloning steps and have low efficiency. To simplify cloning of HDR plasmids, we designed a new plasmid platform, the Janelia Atalanta (pJAT) series, that exploits recent advances in dsDNA synthesis to facilitate Gateway cloning of gRNA sequences and homology arms in one step. Surprisingly, the pJAT plasmids yielded considerably higher HDR efficiency (approximately 25%) than we have observed with other approaches. pJAT plasmids work in multiple Drosophila species and exhibited such high efficiency that previously impossible experiments in Drosophila, such as driving targeted chromosomal inversions, were made possible. We provide pJAT plasmids for a range of commonly performed experiments including targeted insertional mutagenesis, insertion of phiC31-mediated attP landing sites, generation of strains carrying a germ-line source of Cas9, and induction of chromosomal rearrangements. We also provide “empty” pJAT plasmids with multiple cloning sites to simplify construction of plasmids with new functionality. The pJAT platform is generic and may facilitate improved efficiency CRISPR-Cas9 HDR in a wide range of model and non-model organisms.
Fungal small RNAs ride in extracellular vesicles to enter plant cells through clathrin-mediated endocytosis

Small RNAs (sRNAs) of the fungal pathogen Botrytis cinerea can enter plant cells and hijack host Argonaute protein 1 (AGO1) to silence host immunity genes. However, the mechanism by which these fungal sRNAs are secreted and enter host cells remains unclear. Here, we demonstrate that B. cinerea utilizes extracellular vesicles (EVs) to secrete Bc-sRNAs, which are then internalized by plant cells through clathrin-mediated endocytosis (CME). The B. cinerea tetraspanin protein, Punchless 1 (BcPLS1), serves as an EV biomarker and plays an essential role in fungal pathogenicity. We observe numerous Arabidopsis clathrin-coated vesicles (CCVs) around B. cinerea infection sites and the colocalization of B. cinerea EV marker BcPLS1 and Arabidopsis CLATHRIN LIGHT CHAIN 1, one of the core components of CCV. Meanwhile, BcPLS1 and the B. cinerea-secreted sRNAs are detected in purified CCVs after infection. Arabidopsis knockout mutants and inducible dominant-negative mutants of key components of CME pathway exhibit increased resistance to B. cinerea infection. Furthermore, Bc-sRNA loading into Arabidopsis AGO1 and host target gene suppression are attenuated in those CME mutants. Together, our results demonstrate that fungi secrete sRNAs via EVs, which then enter host plant cells mainly through CME.
TFAP2 paralogs regulate midfacial development in part through a conserved ALX genetic pathway

Cranial neural crest development is governed by positional gene regulatory networks (GRNs). Fine-tuning of the GRN components underly facial shape variation, yet how those in the midface are connected and activated remain poorly understood. Here, we show that concerted inactivation of Tfap2a and Tfap2b in the murine neural crest even during the late migratory phase results in a midfacial cleft and skeletal abnormalities. Bulk and single-cell RNA-seq profiling reveal that loss of both Tfap2 members dysregulated numerous midface GRN components involved in midface fusion, patterning, and differentiation. Notably, Alx1/3/4 (Alx) transcript levels are reduced, while ChIP-seq analyses suggest TFAP2 directly and positively regulates Alx gene expression. TFAP2 and ALX co-expression in midfacial neural crest cells of both mouse and zebrafish further implies conservation of this regulatory axis across vertebrates. Consistent with this notion, tfap2a mutant zebrafish present abnormal alx3 expression patterns, and the two genes display a genetic interaction in this species. Together, these data demonstrate a critical role for TFAP2 in regulating vertebrate midfacial development in part through ALX transcription factor gene expression.
Simultaneously sparse and low-rank hyperspectral image recovery from coded aperture compressive measurements via convex optimization

A hyperspectral image (HSI) can be described as a set of images with spatial information across diﬀerent spectral bands. Compressive spectral imaging techniques (CSI) permit to capture a 3-dimensional hyperspectral scene using 2 dimensional coded and multiplexed projections. Recovering the original scene from a very few projections can be valuable in applications such as remote sensing, video surveillance and biomedical imaging. Typically, HSI exhibit high correlations both, in the spatial and spectral dimensions. Thus, exploiting these correlations allows to accurately recover the original scene from compressed measurements. Traditional approaches exploit the sparsity of the scene when represented in a proper basis. For this purpose, an optimization problem that seeks to minimize a joint ℓ2 − ℓ1 norm is solved to obtain the original scene. However, there exist some HSI with an important feature which does not have been widely exploited; HSI are commonly low rank, thus only a few number of spectral signatures are presented in the image. Therefore, this paper proposes an approach to recover a simultaneous sparse and low rank hyperspectral image by exploiting both features at the same time. The proposed approach solves an optimization problem that seeks to minimize the ℓ2-norm, penalized by the ℓ1-norm, to force the solution to be sparse, and penalized by the nuclear norm to force the solution to be low rank. Theoretical analysis along with a set of simulations over diﬀerent data sets show that simultaneously exploiting low rank and sparse structures enhances the performance of the recovery algorithm and the quality of the recovered image with an average improvement of around 3 dB in terms of the peak-signal to noise ratio (PSNR).
Effects of Recent Thermometer Changes in the Cooperative Station Network

During the past five years, the National Weather Service (NWS) has replaced over half of its liquid-in-glass maximum and minimum thermometers in wooden Cotton Region Shelters (CRSs) with thermistor-based Maximum–Minimum Temperature Systems (MMTSs) housed in smaller plastic shelters. Analyses of data from 424 (of the 3300) MMTS stations and 675 CRS stations show that a mean daily minimum temperature change of roughly +0.3°C, a mean daily maximum temperature change of−0.4°C, and a change in average temperature of −0.1 °C were introduced as a result of the new instrumentation. The change of −0.7°C in daily temperature range is particularly significant for climate change studies that use this element as an independent variable. Although troublesome for climatologists, there is reason to believe that this change (relative to older records) represents an improvement in absolute accuracy. The bias appears to be rather sharp and well defined. Since the National Climatic Data Center (NCDC) station history database.
A Cloud Architecture for Emotion Recognition Based on the Appraisal Theory (short paper)

Designing robots with the ability to infer a person’s emotional state represents one of the major challenges in social robotics. This work proposes a cloud system for online human emotion recognition in spontaneous human-robot verbal interaction, structured as a set of REST API endpoints. Based on the appraisal theory of emotion, the system acquires data about the person’s expected appraisal of a given situation, depending on their needs and goals, and combines it with sensory data, such as facial expressions, angles of the head, and gaze of the person, and distance between the person and the robot. The whole set of data is used to infer the person’s emotional state during the interaction through a Random Forest classifier, trained for binary classification (i.e., positive vs. negative emotions). Results confirmed that using both data sources improved performance in both the K-fold and the Leave One Person Out scenarios.
Virtual Sculpting: An Investigation of Directly Manipulated Free-Form Deformation in a Virtual Environment

This thesis presents a Virtual Sculpting system, which addresses the problem of Free-Form Solid Modelling. The disparate elements of a Polygon-Mesh representation, a Directly Manipulated Free-Form Deformation sculpting tool, and a Virtual Environment are drawn into a cohesive whole under the mantle of a clay-sculpting metaphor. This enables a user to mould and manipulate a synthetic solid interactively as if it were composed of malleable clay. The focus of this study is on the interactivity, intuitivity and versatility of such a system. To this end, a range of improvements is investigated which significantly enhances the efficiency and correctness of Directly Manipulated Free-Form Deformation, both separately and as a seamless component of the Virtual Sculpting system.
Active Anchors

Defect detection in steel manufacturing has achieved state-of-the-art results in both localisation and classification of various types of defects, however, this assumes very high-quality datasets that have been verified by domain experts. Labelling such data has become a time-consuming and interaction-heavy task with a great amount of user effort, this is due to variability in the defect characteristics and composite nature. We propose a new acquisition function based on the similarity of defects for refining labels over time by showing the user only the most required to be labelled. We also explore different ways in which to feed these new refinements back into the model to utilize the new knowledge in an effortful way. We achieve this with a graphical interface that provides additional information to the domain expert as the data gets refined, allowing for decision-making with uncertain areas of the steel.
An MA-PPO based Task Scheduling Method for Computing First Networks

Aiming at converging computing and network resources, computing first networking (CFN) provides the computing task scheduling solution along with routing policy based on real-time computing and network information, to achieve the optimal utilization of overall resources and improve user experience. Most of the existing schemes consider computing and network resources separately to obtain their optimal results, lacking a load balancing mechanism that comprehensively considers both. In view of the above, this paper proposes an MA-PPO-based service scheduling algorithm for CFN. Based on the current computing and network resource status, scheduling strategies combined with computing task allocation and routing planning are flexibly generated for each computing task to achieve the overall optimization of computing and network resources utilization. The experimental results show that the algorithm can effectively improve the utilization of computing and network resources, shorten task processing time, and improve user experience.
Mechanisms of lung damage in tuberculosis: implications for chronic obstructive pulmonary disease

Pulmonary tuberculosis is increasingly recognized as a risk factor for COPD. Severe lung function impairment has been reported in post-TB patients. Despite increasing evidence to support the association between TB and COPD, only a few studies describe the immunological basis of COPD among TB patients following successful treatment completion. In this review, we draw on well-elaborated Mycobacterium tuberculosis-induced immune mechanisms in the lungs to highlight shared mechanisms for COPD pathogenesis in the setting of tuberculosis disease. We further examine how such mechanisms could be exploited to guide COPD therapeutics.
Refueling the post COVID-19 brain: potential role of ketogenic medium chain triglyceride supplementation: an hypothesis

COVID-19 infection causes cognitive changes in the acute phase, but also after apparent recovery. Over fifty post (long)-COVID symptoms are described, including cognitive dysfunction (“brain fog”) precluding return to pre-COVID level of function, with rates twice as high in females. Additionally, the predominant demographic affected by these symptoms is younger and still in the workforce. Lack of ability to work, even for six months, has significant socio-economic consequences. This cognitive dysfunction is associated with impaired cerebral glucose metabolism, assessed using 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET), showing brain regions that are abnormal compared to age and sex matched controls. In other cognitive conditions such as Alzheimer’s disease (AD), typical patterns of cerebral glucose hypometabolism, frontal hypometabolism and cerebellar hypermetabolism are common. Similar FDG-PET changes have also been observed in post-COVID-19, raising the possibility of a similar etiology. Ketone bodies (B-hydroxybutyrate, acetoacetate and acetone) are produced endogenously with very low carbohydrate intake or fasting. They improve brain energy metabolism in the face of cerebral glucose hypometabolism in other conditions [mild cognitive impairment (MCI) and AD]. Long-term low carbohydrate intake or prolonged fasting is not usually feasible. Medium chain triglyceride (MCT) is an exogenous route to nutritional ketosis. Research has supported their efficacy in managing intractable seizures, and cognitive impairment in MCI and AD. We hypothesize that cerebral glucose hypometabolism associated with post COVID-19 infection can be mitigated with MCT supplementation, with the prediction that cognitive function would also improve. Although there is some suggestion that post COVID-19 cognitive symptoms may diminish over time, in many individuals this may take more than six months. If MCT supplementation is able to speed the cognitive recovery, this will impact importantly on quality of life. MCT is readily available and, compared to pharmaceutical interventions, is cost-effective. Research shows general tolerability with dose titration. MCT is a component of enteral and parenteral nutrition supplements, including in pediatrics, so has a long record of safety in vulnerable populations. It is not associated with weight gain or adverse changes in lipid profiles. This hypothesis serves to encourage the development of clinical trials evaluating the impact of MCT supplementation on the duration and severity of post COVID-19 cognitive symptoms.