Unsupervised topological analysis of polarized light microscopy: application to quantitative birefringence imaging.

The determination of birefringence (magnitude and axis orientation) of optical materials is of significant interest in various fields. In the case of composite samples, this task becomes complicated and time-consuming; therefore, a partially automated procedure for reconstructing birefringence spatial distribution becomes valuable. Herein, we propose a procedure to reconstruct the spatial distributions of the retardance and optical axis orientation in a geological thin section from sparse quantitative birefringence measurements, using automatic boundary detection on cross-polarized light microscopy images. We examine two particular areas on the selected geological thin section: one that presents a uniaxial crystal with a circular cross-section of its refractive index ellipsoid and the other with grains of varying orientations. The measurement gives the orientation of the grain's optical axis both in and out of the plane of the thin section, which explains the qualitative observations with the cross-polarized light microscope. Future work will connect the measured orientation of the rock thin section with its 3D geological orientation in the field.

Disability reduction following a lumbar stabilization exercise program for low back pain: large vs. small improvement subgroup analyses of physical and psychological variables.

BACKGROUND: Little is known about why patients with low back pain (LBP) respond differently to treatment, and more specifically, to a lumbar stabilization exercise program. As a first step toward answering this question, the present study evaluates how subgroups of patients who demonstrate large and small clinical improvements differ in terms of physical and psychological changes during treatment. METHODS: Participants (n = 110) performed the exercise program (clinical sessions and home exercises) over eight weeks, with 100 retained at six-month follow-up. Physical measures (lumbar segmental instability, motor control impairments, range of motion, trunk muscle endurance and physical performance tests) were collected twice (baseline, end of treatment), while psychological measures (fear-avoidance beliefs, pain catastrophizing, psychological distress, illness perceptions, outcome expectations) were collected at four time points (baseline, mid-treatment, end of treatment, follow-up). The participants were divided into three subgroups (large, moderate and small clinical improvements) based on the change of perceived disability scores. ANOVA for repeated measure compared well-contrasted subgroups (large vs. small improvement) at different times to test for SUBGROUP × TIME interactions. RESULTS: Statistically significant interactions were observed for several physical and psychological measures. In all these interactions, the large- and small-improvement subgroups were equivalent at baseline, but the large-improvement subgroup showed more improvements over time compared to the small-improvement subgroup. For psychological measures only (fear-avoidance beliefs, pain catastrophizing, illness perceptions), between-group differences reached moderate to strong effect sizes, at the end of treatment and follow-up. CONCLUSIONS: The large-improvement subgroup showed more improvement than the small-improvement subgroup with regard to physical factors typically targeted by this specific exercise program as well as for psychological factors that are known to influence clinical outcomes.

Hyperparameter Control Using Fuzzy Logic: Evolving Policies for Adaptive Fuzzy Particle Swarm Optimization Algorithm.

Heuristic optimization methods such as Particle Swarm Optimization depend on their parameters to achieve optimal performance on a given class of problems. Some modifications of heuristic algorithms aim at adapting those parameters during the optimization process. We present a novel approach to design such adaptation strategies using continuous fuzzy feedback control. Fuzzy feedback provides a simple interface where probes are sampled in the optimization process and parameters are fed back to the optimizer. The probes are turned into parameters by a fuzzy process optimized beforehand to maximize performance on a training benchmark. Utilizing this framework, we systematically established 127 different Fuzzy Particle Swarm Optimization algorithms featuring a maximum of 7 parameters under fuzzy control. These newly devised algorithms exhibit superior performance compared to both traditional PSO and some of its best parameter control variants. The performance is reported in the single-objective bound-constrained numerical optimization competition of CEC 2020. Additionally, two specific controls, highlighted for their efficacy and dependability, demonstrated commendable performance in real-world scenarios from CEC 2011.

Towards a Multi-Pixel Photon-to-Digital Converter for Time-Bin Quantum Key Distribution.

We present an integrated single-photon detection device custom designed for quantum key distribution (QKD) with time-bin encoded single photons. We implemented and demonstrated a prototype photon-to-digital converter (PDC) that integrates an 8 × 8 single-photon avalanche diode (SPAD) array with on-chip digital signal processing built in TSMC 65 nm CMOS. The prototype SPADs are used to validate the QKD functionalities with an array of time-to-digital converters (TDCs) to timestamp and process the photon detection events. The PDC uses window gating to reject noise counts and on-chip processing to sort the photon detections into respective time-bins. The PDC prototype achieved a 22.7 ps RMS timing resolution and demonstrated operation in a time-bin setup with 158 ps time-bins at an optical wavelength of 410 nm. This PDC can therefore be an important building block for a QKD receiver and enables compact and robust time-bin QKD systems with imaging detectors.

Zika virus induces massive cytoplasmic vacuolization and paraptosis-like death in infected cells.

The cytopathic effects of Zika virus (ZIKV) are poorly characterized. Innate immunity controls ZIKV infection and disease in most infected patients through mechanisms that remain to be understood. Here, we studied the morphological cellular changes induced by ZIKV and addressed the role of interferon-induced transmembrane proteins (IFITM), a family of broad-spectrum antiviral factors, during viral replication. We report that ZIKV induces massive vacuolization followed by "implosive" cell death in human epithelial cells, primary skin fibroblasts and astrocytes, a phenomenon which is exacerbated when IFITM3 levels are low. It is reminiscent of paraptosis, a caspase-independent, non-apoptotic form of cell death associated with the formation of large cytoplasmic vacuoles. We further show that ZIKV-induced vacuoles are derived from the endoplasmic reticulum (ER) and dependent on the PI3K/Akt signaling axis. Inhibiting the Sec61 ER translocon in ZIKV-infected cells blocked vacuole formation and viral production. Our results provide mechanistic insight behind the ZIKV-induced cytopathic effect and indicate that IFITM3, by acting as a gatekeeper for incoming virus, restricts virus takeover of the ER and subsequent cell death.

3D Photon-to-Digital Converter for Radiation Instrumentation: Motivation and Future Works.

Analog and digital SiPMs have revolutionized the field of radiation instrumentation by replacing both avalanche photodiodes and photomultiplier tubes in many applications. However, multiple applications require greater performance than the current SiPMs are capable of, for example timing resolution for time-of-flight positron emission tomography and time-of-flight computed tomography, and mitigation of the large output capacitance of SiPM array for large-scale time projection chambers for liquid argon and liquid xenon experiments. In this contribution, the case will be made that 3D photon-to-digital converters, also known as 3D digital SiPMs, have a potentially superior performance over analog and 2D digital SiPMs. A review of 3D photon-to-digital converters is presented along with various applications where they can make a difference, such as time-of-flight medical imaging systems and low-background experiments in noble liquids. Finally, a review of the key design choices that must be made to obtain an optimized 3D photon-to-digital converter for radiation instrumentation, more specifically the single-photon avalanche diode array, the CMOS technology, the quenching circuit, the time-to-digital converter, the digital signal processing and the system level integration, are discussed in detail.

Characterization of E3 ligases involved in lysosomal sorting of the HIV-1 restriction factor BST2.

The cellular protein BST2 (also known as tetherin) acts as a major intrinsic antiviral protein that prevents the release of enveloped viruses by trapping nascent viral particles at the surface of infected cells. Viruses have evolved specific strategies to displace BST2 from viral budding sites in order to promote virus egress. In HIV-1, the accessory protein Vpu counters BST2 antiviral activity and promotes sorting of BST2 for lysosomal degradation. Vpu increases polyubiquitylation of BST2, a post-translation modification required for Vpu-induced BST2 downregulation, through recruitment of the E3 ligase complex SCF adaptors ß-TrCP1 and ß-TrCP2 (two isoforms encoded by BTRC and FBXW11, respectively). Herein, we further investigate the role of the ubiquitylation machinery in the lysosomal sorting of BST2. Using a small siRNA screen, we highlighted two additional regulators of BST2 constitutive ubiquitylation and sorting to the lysosomes: the E3 ubiquitin ligases NEDD4 and MARCH8. Interestingly, Vpu does not hijack the cellular machinery that is constitutively involved in BST2 ubiquitylation to sort BST2 for degradation in the lysosomes but instead promotes the recognition of BST2 by ß-TrCP proteins. Altogether, our results provide further understanding of the mechanisms underlying BST2 turnover in cells.

Natural mutations in IFITM3 modulate post-translational regulation and toggle antiviral specificity.

The interferon-induced transmembrane (IFITM) proteins protect host cells from diverse virus infections. IFITM proteins also incorporate into HIV-1 virions and inhibit virus fusion and cell-to-cell spread, with IFITM3 showing the greatest potency. Here, we report that amino-terminal mutants of IFITM3 preventing ubiquitination and endocytosis are more abundantly incorporated into virions and exhibit enhanced inhibition of HIV-1 fusion. An analysis of primate genomes revealed that IFITM3 is the most ancient antiviral family member of the IFITM locus and has undergone a repeated duplication in independent host lineages. Some IFITM3 genes in nonhuman primates, including those that arose following gene duplication, carry amino-terminal mutations that modify protein localization and function. This suggests that "runaway" IFITM3 variants could be selected for altered antiviral activity. Furthermore, we show that adaptations in IFITM3 result in a trade-off in antiviral specificity, as variants exhibiting enhanced activity against HIV-1 poorly restrict influenza A virus. Overall, we provide the first experimental evidence that diversification of IFITM3 genes may boost the antiviral coverage of host cells and provide selective functional advantages.

Regional variations in vascular density correlate with resting-state and task-evoked blood oxygen level-dependent signal amplitude.

Functional magnetic resonance imaging (fMRI) has become one of the primary tools used for noninvasively measuring brain activity in humans. For the most part, the blood oxygen level-dependent (BOLD) contrast is used, which reflects the changes in hemodynamics associated with active brain tissue. The main advantage of the BOLD signal is that it is relatively easy to measure and thus is often used as a proxy for comparing brain function across population groups (i.e., control vs. patient). However, it is particularly weighted toward veins whose structural architecture is known to vary considerably across the brain. This makes it difficult to interpret whether differences in BOLD between cortical areas reflect true differences in neural activity or vascular structure. We therefore investigated how regional variations of vascular density (VAD) relate to the amplitude of resting-state and task-evoked BOLD signals. To address this issue, we first developed an automated method for segmenting veins in images acquired with susceptibility-weighted imaging, allowing us to visualize the venous vascular tree across the brain. In 19 healthy subjects, we then applied voxel-based morphometry (VBM) to T1-weighted images and computed regional measures of gray matter density (GMD). We found that, independent of spatial scale, regional variations in resting-state and task-evoked fMRI amplitudes were better correlated to VAD compared to GMD. Using a general linear model (GLM), it was observed that the bulk of regional variance in resting-state activity could be modeled by VAD. Cortical areas whose resting-state activity was most suppressed by VAD correction included Cuneus, Precuneus, Culmen, and BA 9, 10, and 47. Taken together, our results suggest that resting-state BOLD signals are significantly related to the underlying structure of the brain vascular system. Calibrating resting BOLD activity by venous structure may result in a more accurate interpretation of differences observed between cortical areas and/or individuals.

Paper features: a neglected source of information for letter recognition.

Adult observers have surprisingly low calculation efficiencies for letter recognition (see, e.g., Pelli, Burns, Farell, & Moore-Page, 2006). Here, we examine the possibility that this is partly due to observers' neglecting paper features (e.g., the absence of ascenders and descenders in 'o'). Each of 16 observers completed 5,000 trials of a single-letter two-alternative forced-choice detection task. Using a combination of classification image analyses and Bayesian statistical analyses, we argue that between 60% and 75% of our participants indeed neglected paper features.

Exploring the impact of violence in video games.

Playing a violent game for a few weeks did not alter neural and behavioral responses to the pain of others in inexperienced male gamers.

Reading laterally: the cerebral hemispheric use of spatial frequencies in visual word recognition.

It is generally accepted that the left hemisphere (LH) is more capable for reading than the right hemisphere (RH). Left hemifield presentations (initially processed by the RH) lead to a globally higher error rate, slower word identification, and a significantly stronger word length effect (i.e., slower reaction times for longer words). Because the visuo-perceptual mechanisms of the brain for word recognition are primarily localized in the LH (Cohen et al., 2003), it is possible that this part of the brain possesses better spatial frequency (SF) tuning for processing the visual properties of words than the RH. The main objective of this study is to determine the SF tuning functions of the LH and RH for word recognition. Each word image was randomly sampled in the SF domain using the SF bubbles method (Willenbockel et al., 2010) and was presented laterally to the left or right visual hemifield. As expected, the LH requires less visual information than the RH to reach the same level of performance, illustrating the well-known LH advantage for word recognition. Globally, the SF tuning of both hemispheres is similar. However, these seemingly identical tuning functions hide important differences. Most importantly, we argue that the RH requires higher SFs to identify longer words because of crowding.

Secondary ion mass spectrometry, a powerful tool for revealing ink formulations and animal skins in medieval manuscripts.

Book production by medieval scriptoria have gained growing interest in recent studies. In this context, identifying ink compositions and parchment animal species from illuminated manuscripts is of great importance. Here, we introduce time-of-flight secondary ion mass spectrometry (ToF-SIMS) as a non-invasive tool to identify both inks and animal skins in manuscripts, at the same time. For this purpose, both positive and negative ion spectra in inked and non-inked areas were recorded. Chemical compositions of pigments (decoration) or black inks (text) were determined by searching for characteristic ion mass peaks. Animal skins were identified by data processing of raw ToF-SIMS spectra using principal component analysis (PCA). In illuminated manuscripts from the fifteenth to sixteenth century, malachite (green), azurite (blue), cinnabar (red) inorganic pigments, as well as iron-gall black ink, were identified. Carbon black and indigo (blue) organic pigments were also identified. Animal skins were identified in modern parchments of known animal species by a two-step PCA procedure. We believe the proposed method will find extensive application in material studies of medieval manuscripts, as it is non-invasive, highly sensitive and able to identify both inks and animal skins at the same time, even from traces of pigments and tiny scanned areas.

Derivation of clinical prediction rules for identifying patients with non-acute low back pain who respond best to a lumbar stabilization exercise program at post-treatment and six-month follow-up.

Low back pain (LBP) remains one of the most common and incapacitating health conditions worldwide. Clinical guidelines recommend exercise programs after the acute phase, but clinical effects are modest when assessed at a population level. Research needs to determine who is likely to benefit from specific exercise interventions, based on clinical presentation. This study aimed to derive clinical prediction rules (CPRs) for treatment success, using a lumbar stabilization exercise program (LSEP), at the end of treatment and at six-month follow-up. The eight-week LSEP, including clinical sessions and home exercises, was completed by 110 participants with non-acute LBP, with 100 retained at the six-month follow-up. Physical (lumbar segmental instability, motor control impairments, posture and range of motion, trunk muscle endurance and physical performance tests) and psychological (related to fear-avoidance and home-exercise adherence) measures were collected at a baseline clinical exam. Multivariate logistic regression models were used to predict clinical success, as defined by ≥50% decrease in the Oswestry Disability Index. CPRs were derived for success at program completion (T8) and six-month follow-up (T34), negotiating between predictive ability and clinical usability. The chosen CPRs contained four (T8) and three (T34) clinical tests, all theoretically related to spinal instability, making these CPRs specific to the treatment provided (LSEP). The chosen CPRs provided a positive likelihood ratio of 17.9 (T8) and 8.2 (T34), when two or more tests were positive. When applying these CPRs, the probability of treatment success rose from 49% to 96% at T8 and from 53% to 92% at T34. These results support the further development of these CPRs by proceeding to the validation stage.

The Tactile-Visual Conflict Processing and Its Modulation by Tactile-Induced Emotional States: An Event-Related Potential Study.

This experiment used event-related potentials (ERPs) to study the tactile-visual information conflict processing in a tactile-visual pairing task and its modulation by tactile-induced emotional states. Eighteen participants were asked to indicate whether the tactile sensation on their body matched or did not match the expected tactile sensation associated with the object depicted in an image. The type of tactile-visual stimuli (matched vs. mismatched) and the valence of tactile-induced emotional states (positive vs. negative) were manipulated following a 2 × 2 factorial design. Electrophysiological analyses revealed a mismatched minus matched negative difference component between 420 and 620 ms after stimulus onset in the negative tactile-induced emotional state condition. This ND420-620 component was considered as a sign of the cross-modal conflict processing during the processing of incongruent tactile-visual information. In contrast, no significant mismatched minus matched negative difference component was found in the positive tactile-induced emotional state condition. Together, these results support the hypothesis that a positive emotional state induced by a positive tactile stimulation improves tactile-visual conflict processing abilities.

Event-Related Brain Potentials Associated With the Olfactory-Visual Stroop Effect and Its Modulation by Olfactory-Induced Emotional States.

This study investigated the event-related brain potentials associated with the olfactory-visual cross-modal Stroop effect and its modulation by olfactory-induced and self-reported affective states. Eighteen healthy participants were presented with an olfactory stimulus and the image of a plant, and they had to categorize the olfactory attribute of the image as "aromatic" or "pungent" by pressing the relevant button as quickly as possible. The type of olfactory-visual stimuli (congruent or incongruent) and the valence of the olfactory-induced emotional states (positive or negative) were manipulated following a 2 × 2 factorial design. Interference effects were observed at the behavioral and the electrophysiological levels: response times recorded in the incongruent condition were higher than those observed in the congruent condition; an incongruent minus congruent negative difference component was discovered between 350 and 550 ms after stimulus onset in the negative-but not in the positive-olfactory-induced emotional state condition. This ND350-550 component was interpreted as reflecting the amount of selective attention involved in the olfactory-visual cross-modal Stroop effect. These results are also consistent with a facilitatory effect of positive emotional state on selective attention which could reduce brain potentials associated with the cross-modal interference effect.

Uncovering gender discrimination cues in a realistic setting.

Which face cues do we use for gender discrimination? Few studies have tried to answer this question and the few that have tried typically used only a small set of grayscale stimuli, often distorted and presented a large number of times. Here, we reassessed the importance of facial cues for gender discrimination in a more realistic setting. We applied Bubbles-a technique that minimizes bias toward specific facial features and does not necessitate the distortion of stimuli-to a set of 300 color photographs of Caucasian faces, each presented only once to 30 participants. Results show that the region of the eyes and the eyebrows-probably in the light-dark channel-is the most important facial cue for accurate gender discrimination; and that the mouth region is driving fast correct responses (but not fast incorrect responses)-the gender discrimination information in the mouth region is concentrated in the red-green color channel. Together, these results suggest that, when color is informative in the mouth region, humans use it and respond rapidly; and, when it's not informative, they have to rely on the more robust but more sluggish luminance information in the eye-eyebrow region.

Inducing the use of right eye enhances face-sex categorization performance.

Face recognition ability varies tremendously among neurologically typical individuals. What causes these differences is still largely unknown. Here, we first used a data-driven experimental technique-bubbles-to measure the use of local facial information in 140 neurotypical individuals during a face-sex categorization task. We discovered that the use of the eye and eyebrow area located on the right side of the face image from the observer's viewpoint correlates positively with performance, whereas the use of the left-eye and eyebrow area correlates negatively with performance. We then tested if performance could be altered by inducing participants to use either the right- or the left-eye area. One hundred of these participants thus underwent a 1-hr session of a novel implicit training procedure aimed at inducing the use of specific facial information. Afterward, participants repeated the bubbles face-sex categorization task to assess the changes in use of information and its effect on performance. Participants that underwent right-eye induction used this facial region more than they initially did and, as expected, improved their performance more than the participants who underwent the left-eye induction. This is the first clear evidence of a causal link between the use of specific face information and face recognition ability: Use of right-eye region not only predicts but causes better face-sex categorization. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

The Neural Basis of Taste-visual Modal Conflict Control in Appetitive and Aversive Gustatory Context.

The functional magnetic resonance imaging (fMRI) technique was used to investigate brain activations related to conflict control in a taste-visual cross-modal pairing task. On each trial, participants had to decide whether the taste of a gustatory stimulus matched or did not match the expected taste of the food item depicted in an image. There were four conditions: Negative match (NM; sour gustatory stimulus and image of sour food), negative mismatch (NMM; sour gustatory stimulus and image of sweet food), positive match (PM; sweet gustatory stimulus and image of sweet food), positive mismatch (PMM; sweet gustatory stimulus and image of sour food). Blood oxygenation level-dependent (BOLD) contrasts between the NMM and the NM conditions revealed an increased activity in the middle frontal gyrus (MFG) (BA 6), the lingual gyrus (LG) (BA 18), and the postcentral gyrus. Furthermore, the NMM minus NM BOLD differences observed in the MFG were correlated with the NMM minus NM differences in response time. These activations were specifically associated with conflict control during the aversive gustatory stimulation. BOLD contrasts between the PMM and the PM condition revealed no significant positive activation, which supported the hypothesis that the human brain is especially sensitive to aversive stimuli. Altogether, these results suggest that the MFG is associated with the taste-visual cross-modal conflict control. A possible role of the LG as an information conflict detector at an early perceptual stage is further discussed, along with a possible involvement of the postcentral gyrus in the processing of the taste-visual cross-modal sensory contrast.

Perceptual learning without signal.

Perceptual learning is characterized by an improvement in a perceptual task following practice. Several studies have demonstrated that top-down processes, such as attention and task-related expectations, can be necessary components of perceptual learning [Ahissar & Hochstein, 1993, 2000, 2002; Fahle & Morgan, 1996; Seitz, Lefebvre, Watanabe, & Jolicoeur, 2005; Seitz, Nanez, Holloway, Koyama, & Watanabe, 2005; Seitz & Watanabe, 2003; Shiu & Pashler, 1992]. Here, we report an experiment that isolated top-down processes in perceptual learning, using a variant of the Gosselin and Schyns (1992) no-signal procedure. Results indicate that top-down processes can be sufficient to produce substantial, possibly long-lasting and rotation-invariant perceptual learning.