Haze limits visibility and reduces image contrast in outdoor images. The degradation is different for every pixel and depends on the distance of the scene point from the camera. This dependency is ...expressed in the transmission coefficients, that control the scene attenuation and amount of haze in every pixel. Previous methods solve the single image dehazing problem using various patch-based priors. We, on the other hand, propose an algorithm based on a new, non-local prior. The algorithm relies on the assumption that colors of a haze-free image are well approximated by a few hundred distinct colors, that form tight clusters in RGB space. Our key observation is that pixels in a given cluster are often non-local, i.e., they are spread over the entire image plane and are located at different distances from the camera. In the presence of haze these varying distances translate to different transmission coefficients. Therefore, each color cluster in the clear image becomes a line in RGB space, that we term a haze-line. Using these haze-lines, our algorithm recovers both the distance map and the haze-free image. The algorithm is linear in the size of the image, deterministic and requires no training. It performs well on a wide variety of images and is competitive with other stateof-the-art methods.
Magnitude integration in the Archerfish Leibovich-Raveh, Tali; Raveh, Ashael; Vilker, Dana ...
Scientific reports,
08/2021, Volume:
11, Issue:
1
Journal Article
Peer reviewed
Open access
We make magnitude-related decisions every day, for example, to choose the shortest queue at the grocery store. When making such decisions, which magnitudes do we consider? The dominant theory ...suggests that our focus is on numerical quantity, i.e., the number of items in a set. This theory leads to quantity-focused research suggesting that discriminating quantities is automatic, innate, and is the basis for mathematical abilities in humans. Another theory suggests, instead, that non-numerical magnitudes, such as the total area of the compared items, are usually what humans rely on, and numerical quantity is used only when required. Since wild animals must make quick magnitude-related decisions to eat, seek shelter, survive, and procreate, studying which magnitudes animals spontaneously use in magnitude-related decisions is a good way to study the relative primacy of numerical quantity versus non-numerical magnitudes. We asked whether, in an animal model, the influence of non-numerical magnitudes on performance in a spontaneous magnitude comparison task is modulated by the number of non-numerical magnitudes that positively correlate with numerical quantity. Our animal model was the Archerfish, a fish that, in the wild, hunts insects by shooting a jet of water at them. These fish were trained to shoot water at artificial targets presented on a computer screen above the water tank. We tested the Archerfish's performance in spontaneous, untrained two-choice magnitude decisions. We found that the fish tended to select the group containing larger non-numerical magnitudes and smaller quantities of dots. The fish selected the group containing more dots mostly when the quantity of the dots was positively correlated with all five different non-numerical magnitudes. The current study adds to the body of studies providing direct evidence that in some cases animals' magnitude-related decisions are more affected by non-numerical magnitudes than by numerical quantity, putting doubt on the claims that numerical quantity perception is the most basic building block of mathematical abilities.
Variational inference provides a way to approximate probability densities through optimization. It does so by optimizing an upper or a lower bound of the likelihood of the observed data (the ...evidence). The classic variational inference approach suggests maximizing the Evidence Lower Bound (ELBO). Recent studies proposed to optimize the variational Rényi bound (VR) and the χ upper bound. However, these estimates, which are based on the Monte Carlo (MC) approximation, either underestimate the bound or exhibit a high variance. In this work, we introduce a new upper bound, termed the Variational Rényi Log Upper bound (VRLU), which is based on the existing VR bound. In contrast to the existing VR bound, the MC approximation of the VRLU bound maintains the upper bound property. Furthermore, we devise a (sandwiched) upper–lower bound variational inference method, termed the Variational Rényi Sandwich (VRS), to jointly optimize the upper and lower bounds. We present a set of experiments, designed to evaluate the new VRLU bound and to compare the VRS method with the classic Variational Autoencoder (VAE) and the VR methods. Next, we apply the VRS approximation to the Multiple-Source Adaptation problem (MSA). MSA is a real-world scenario where data are collected from multiple sources that differ from one another by their probability distribution over the input space. The main aim is to combine fairly accurate predictive models from these sources and create an accurate model for new, mixed target domains. However, many domain adaptation methods assume prior knowledge of the data distribution in the source domains. In this work, we apply the suggested VRS density estimate to the Multiple-Source Adaptation problem (MSA) and show, both theoretically and empirically, that it provides tighter error bounds and improved performance, compared to leading MSA methods.
p105 plays dual roles in NF-κB signaling: it generates the active subunit p50 and in its precursor form inhibits NF-κB activation. p105 processing occurs under basal conditions and increases ...following signaling. IκB kinase β (IKKβ) mediates phosphorylation at the C-terminal domain of p105, leads to accelerated processing and degradation of the precursor. A20 is a dual function deubiquitinating and ubiquitin ligating enzyme, involving in turning-off the NF-κB signaling pathway. Here we show that A20 suppresses TNFα-induced proteolysis of p105. We demonstrate that A20 inhibits both the signal induced processing and the degradation of p105 upstream to IKK stimulation. In addition, A20 represses the constitutive processing of the precursor protein in IKK independent manner. Silencing of A20 in cells by siRNA, restores p105 processing and the generation of p50. Functional analysis of A20, shows that the ubiquitin ligase activity mediated by its zinc finger domain (ZF), is required for the basal processing inhibitory effect. Its N-terminal ovarian tumor (OTU) domain, however, is not obligatory. We show that A20 inhibits p50 generation in cells by reducing the ubiquitination of its precursor, p105. Co-immunoprecipitation experiments show that A20 is immunoprecipitated by p105 only in the presence of its recently identified ligase, KPC1. Our data propose an additional novel mechanism to explain the known NF-κB inhibitory effects of A20: by affecting p105 ubiquitination and subsequently its degradation and limited processing.
•A20 inhibits the signal induced proteolysis of p105 upstream to IKK activation.•A20 inhibits the basal processing of the NF-κB p105 precursor.•The mechanism relies on the integrity of the ubiquitin ligase activity of A20.
A host-protein score (BV score) that combines the circulating levels of TNF-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein 10 (IP-10) and C-reactive protein (CRP) was ...developed for distinguishing bacterial from viral infection. This study assessed the potential of the BV score to impact decision making and antibiotic stewardship at the emergency department (ED), by comparing BV score's performance to physician's etiological suspicion at patient presentation.
Rosetta study participants, aged 3 months to 18 years with febrile respiratory tract infection or fever without source, were prospectively recruited in a tertiary care pediatric ED. 465 patients were recruited, 298 met eligibility criteria and 287 were enrolled. ED physician's etiological suspicion was recorded in a questionnaire. BV score was measured retrospectively with results interpreted as viral, bacterial or equivocal and compared to reference standard etiology, which was adjudicated by three independent experts based on all available data. Experts were blinded to BV scores.
Median age was 1.3 years (interquartile range 1.7), 39.7% females. 196 cases were reference standard viral and 18 cases were reference standard bacterial. BV score attained sensitivity of 88.9% (95% confidence interval: 74.4-100), specificity 92.1% (88.1-96.0), positive predictive value 53.3% (35.5-71.2) and negative predictive value 98.8% (97.1-100). Positive likelihood ratio was 11.18 (6.59-18.97) and negative likelihood ratio was 0.12 (0.03-0.45). The rate of BV equivocal scores was 9.4%. Comparing physician's suspicion to BV score and to the reference standard, and assuming full adoption, BV score could potentially correct the physician's diagnosis and reduce error ~2-fold, from 15.9% to 8.2%.
BV score has potential to aid the diagnostic process. Future studies are warranted to assess the impact of real-time BV results on ED practice.
Both DNA- and RNA-based nanotechnologies are remarkably useful for the engineering of molecular devices in vitro and are applied in a vast collection of applications. Yet, the ability to integrate ...functional nucleic acid nanostructures in applications outside of the lab requires overcoming their inherent degradation sensitivity and subsequent loss of function. Viruses are minimalistic yet sophisticated supramolecular assemblies, capable of shielding their nucleic acid content in nuclease-rich environments. Inspired by this natural ability, we engineered RNA-virus-like particles (VLPs) nanocarriers (NCs). We showed that the VLPs can function as an exceptional protective shell against nuclease-mediated degradation. We then harnessed biological recognition elements and demonstrated how engineered riboswitch NCs can act as a possible disease-modifying treatment for genetic metabolic disorders. The functional riboswitch is capable of selectively and specifically binding metabolites and preventing their self-assembly process and its downstream effects. When applying the riboswitch nanocarriers to an in vivo yeast model of adenine accumulation and self-assembly, significant inhibition of the sensitivity to adenine feeding was observed. In addition, using an amyloid-specific dye, we proved the riboswitch nanocarriers’ ability to reduce the level of intracellular amyloid-like metabolite cytotoxic structures. The potential of this RNA therapeutic technology does not apply only to metabolic disorders, as it can be easily fine-tuned to be applied to other conditions and diseases.
Complex mixtures, characterized by high density of compounds, challenge trace detection and identification. This is further exacerbated in nontargeted analysis, where a compound of interest may be ...well hidden under thousands of matrix compounds. We studied the effect of matrix complexity on nontargeted detection (peak picking) by LC–MS/MS (Orbitrap) analysis. A series of ∼20 drugs, V-type chemical warfare agents and pesticides, simulating toxic unknowns, were spiked at various concentrations in several complex matrices including urine, rosemary leaves, and soil extracts. Orbitrap “TraceFinder” software was used to explore their peak intensities in relation to the matrix (peak location in an intensity-sorted list). Average practical detection limits of nontargets were determined. While detection among the first 10,000 peaks was achieved at 0.3–1 ng/mL levels in the extract, for the more realistic “top 1000” list, much higher concentrations were required, approaching 10–30 ng/mL. A negative power law functional dependence between the peak location in an intensity-sorted suspect list and the nontarget concentration is proposed. Controlled complexity was explored with a series of urine dilutions, resulting in an excellent correlation between the power law coefficient and dilution factor. The intensity distribution of matrix peaks was found to spread (unevenly) on a broad range, fitting well the Weibull distribution function with all matrices and extracts. The quantitative approach demonstrated here gives a measure of the actual capabilities and limitations of LC–MS in the analysis of nontargets in complex matrices. It may be used to estimate and compare the complexity of matrices and predict the typical detection limits of unknowns.
The formation of amyloid-like structures by metabolites is associated with several inborn errors of metabolism (IEMs). These structures display most of the biological, chemical and physical ...properties of protein amyloids. However, the molecular interactions underlying the assembly remain elusive, and so far, no modulating therapeutic agents are available for clinical use. Chemical chaperones are known to inhibit protein and peptide amyloid formation and stabilize misfolded enzymes. Here, we provide an in-depth characterization of the inhibitory effect of osmolytes and hydrophobic chemical chaperones on metabolite assemblies, thus extending their functional repertoire. We applied a combined in vivo-in vitro-in silico approach and show their ability to inhibit metabolite amyloid-induced toxicity and reduce cellular amyloid content in yeast. We further used various biophysical techniques demonstrating direct inhibition of adenine self-assembly and alteration of fibril morphology by chemical chaperones. Using a scaffold-based approach, we analyzed the physiochemical properties of various dimethyl sulfoxide derivatives and their role in inhibiting metabolite self-assembly. Lastly, we employed whole-atom molecular dynamics simulations to elucidate the role of hydrogen bonds in osmolyte inhibition. Our results imply a dual mode of action of chemical chaperones as IEMs therapeutics, that could be implemented in the rational design of novel lead-like molecules.
Fentanyl and its non‐pharmaceutical analogues (NPFs) are potent synthetic opioids, traditionally used for pain management, with ever‐increasing illicit uses. Tightening the regulation for known ...fentanyls leads to new synthetic analogues in the opioid market. Furthermore, the Organization for the Prohibition of Chemical Weapons (OPCW) has recently issued a decision regarding aerosolized use of central nervous system (CNS)‐acting agents, such as fentanyl and its analogues, under the concern that these materials could be misused for terror or war purposes. The ever‐increasing development of new fentanyl analogues makes the task of detection and identification of these new, unknown analogues crucial. In this work, we introduce an automated tool for the detection and putative identification of “unknown” fentanyl analogues, using liquid chromatography–mass spectrometry (LC–MS) (high‐resolution mass spectrometry HRMS) analysis, subsequently followed by data processing using the “Compound Discoverer” software. This software, in our modified use, enabled the automatic detection of various fentanyl analogues, by “digging” out components and comparing them to pre‐calculated theoretical molecular ions of possible modifications or transformations on the fentanyl backbone structure (no library or database used). Subsequently, structural elucidation for the proposed component of interest is carried out by automated MS/MS data interpretation, as performed by the software. This method was explored on 12 fentanyl‐based “unknown” analogues used as model examples, including chemical modifications such as fluorination and methylation. In all tested compounds, automatic detection and identification were achieved, even at concentrations as low as 1 ng/mL in an environmental soil matrix extract.
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•A Mediterranean and low carbohydrate diet decreases hepatic fat more than a low-fat diet, beyond visceral fat changes.•Decreases in hepatic fat are independently associated with ...specific improved parameters.•The beneficial effect of a Mediterranean diet over a low-fat diet is mainly mediated by decreases in hepatic fat.
It is unclear if a reduction in hepatic fat content (HFC) is a major mediator of the cardiometabolic benefit of lifestyle intervention, and whether it has prognostic significance beyond the loss of visceral adipose tissue (VAT). In the present sub-study, we hypothesized that HFC loss in response to dietary interventions induces specific beneficial effects independently of VAT changes.
In an 18-month weight-loss trial, 278 participants with abdominal obesity/dyslipidemia were randomized to low-fat (LF) or Mediterranean/low-carbohydrate (MED/LC + 28 g walnuts/day) diets with/without moderate physical activity. HFC and abdominal fat-depots were measured using magnetic resonance imaging at baseline, after 6 (sub-study, n = 158) and 18 months.
Of 278 participants (mean HFC 10.2% range: 0.01%–50.4%), the retention rate was 86.3%. The %HFC substantially decreased after 6 months (−6.6% absolute units −41% relatively) and 18 months (−4.0% absolute units −29% relatively; p <0.001 vs. baseline). Reductions of HFC were associated with decreases in VAT beyond weight loss. After controlling for VAT loss, decreased %HFC remained independently associated with reductions in serum gamma glutamyltransferase and alanine aminotransferase, circulating chemerin, and glycated hemoglobin (p <0.05). While the reduction in HFC was similar between physical activity groups, MED/LC induced a greater %HFC decrease (p = 0.036) and greater improvements in cardiometabolic risk parameters (p <0.05) than the LF diet, even after controlling for VAT changes. Yet, the greater improvements in cardiometabolic risk parameters induced by MED/LC were all markedly attenuated when controlling for HFC changes.
%HFC is substantially reduced by diet-induced moderate weight loss and is more effectively reduced by the MED/LC diet than the LF diet, independently of VAT changes. The beneficial effects of the MED/LC diet on specific cardiometabolic parameters appear to be mediated more by decreases in %HFC than VAT loss.
High hepatic fat content is associated with metabolic syndrome, type 2 diabetes mellitus, and coronary heart disease. In the CENTRAL 18-month intervention trial, a Mediterranean/low-carbohydrate diet induced a greater decrease in hepatic fat content than a low-fat diet, conferring beneficial health effects that were beyond the favorable effects of visceral fat loss.
ClinicalTrials.gov Identifier: NCT01530724.
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