Showing papers by "Bar-Ilan University published in 2021"

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

Abstract: In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients

Abstract: The gut microbiome has been shown to influence the response of tumors to anti-PD-1 (programmed cell death-1) immunotherapy in preclinical mouse models and observational patient cohorts. However, modulation of gut microbiota in cancer patients has not been investigated in clinical trials. In this study, we performed a phase 1 clinical trial to assess the safety and feasibility of fecal microbiota transplantation (FMT) and reinduction of anti-PD-1 immunotherapy in 10 patients with anti-PD-1-refractory metastatic melanoma. We observed clinical responses in three patients, including two partial responses and one complete response. Notably, treatment with FMT was associated with favorable changes in immune cell infiltrates and gene expression profiles in both the gut lamina propria and the tumor microenvironment. These early findings have implications for modulating the gut microbiota in cancer treatment.

Population Properties of Compact Objects from the Second LIGO-Virgo Gravitational-Wave Transient Catalog

Abstract: We report on the population of 47 compact binary mergers detected with a false-alarm rate of 0.01 are dynamically assembled. Third, we estimate merger rates, finding RBBH = 23.9-+8.614.3 Gpc-3 yr-1 for BBHs and RBNS = 320-+240490 Gpc-3 yr-1 for binary neutron stars. We find that the BBH rate likely increases with redshift (85% credibility) but not faster than the star formation rate (86% credibility). Additionally, we examine recent exceptional events in the context of our population models, finding that the asymmetric masses of GW190412 and the high component masses of GW190521 are consistent with our models, but the low secondary mass of GW190814 makes it an outlier.

Observation of Gravitational Waves from Two Neutron Star–Black Hole Coalescences

Abstract: We report the observation of gravitational waves from two compact binary coalescences in LIGO’s and Virgo’s third observing run with properties consistent with neutron star–black hole (NSBH) binaries. The two events are named GW200105_162426 and GW200115_042309, abbreviated as GW200105 and GW200115; the first was observed by LIGO Livingston and Virgo and the second by all three LIGO–Virgo detectors. The source of GW200105 has component masses 8.9−1.5+1.2 and 1.9−0.2+0.3M⊙ , whereas the source of GW200115 has component masses 5.7−2.1+1.8 and 1.5−0.3+0.7M⊙ (all measurements quoted at the 90% credible level). The probability that the secondary’s mass is below the maximal mass of a neutron star is 89%–96% and 87%–98%, respectively, for GW200105 and GW200115, with the ranges arising from different astrophysical assumptions. The source luminosity distances are 280−110+110 and 300−100+150Mpc , respectively. The magnitude of the primary spin of GW200105 is less than 0.23 at the 90% credible level, and its orientation is unconstrained. For GW200115, the primary spin has a negative spin projection onto the orbital angular momentum at 88% probability. We are unable to constrain the spin or tidal deformation of the secondary component for either event. We infer an NSBH merger rate density of 45−33+75Gpc−3yr−1 when assuming that GW200105 and GW200115 are representative of the NSBH population or 130−69+112Gpc−3yr−1 under the assumption of a broader distribution of component masses.

Aging in Times of the COVID-19 Pandemic: Avoiding Ageism and Fostering Intergenerational Solidarity.

Abstract: 1School of Social Work, Bar Ilan University, Ramat Gan, Israel. 2Department of Psychology, University of Toronto, Ontario, Canada. 3Department of Human Development and Family Studies, Colorado State University, Fort Collins. 4Social and Behavioral Sciences Department, Yale School of Public Health, New Haven, Connecticut. 5Department of Psychology, North Carolina State University, Raleigh. 6Department of Psychology, Friedrich-Schiller-University Jena, Germany. 7German Centre of Gerontology, Berlin, Germany. 8Network of Aging Research, Heidelberg University, Germany.

Impact of age, ethnicity, sex and prior infection status on immunogenicity following a single dose of the BNT162b2 mRNA COVID-19 vaccine: real-world evidence from healthcare workers, Israel, December 2020 to January 2021.

Abstract: The BNT162b2 mRNA COVID-19 vaccine showed high efficacy in clinical trials but observational data from populations not included in trials are needed. We describe immunogenicity 21 days post-dose 1 among 514 Israeli healthcare workers by age, ethnicity, sex and prior COVID-19 infection. Immunogenicity was similar by ethnicity and sex but decreased with age. Those with prior infection had antibody titres one magnitude order higher than naive individuals regardless of the presence of detectable IgG antibodies pre-vaccination.

Predicting intention to receive COVID-19 vaccine among the general population using the health belief model and the theory of planned behavior model.

Abstract: This study aim to explore the intentions, motivators and barriers of the general public to vaccinate against COVID-19, using both the Health Belief Model (HBM) and the Theory of Planned Behavior (TPB) model. An online survey was conducted among Israeli adults aged 18 years and older from May 24 to June 24, 2020. The survey included socio-demographic and health-related questions, questions related to HBM and TPB dimensions, and intention to receive a COVID-19 vaccine. Associations between questionnaire variables and COVID-19 vaccination intention were assessed by univariate and multivariate analyses. Eighty percent of 398 eligible respondents stated their willingness to receive COVID-19 vaccine. A unified model including HBM and TPB predictor variables as well as demographic and health-related factors, proved to be a powerful predictor of intention to receive COVID-19 vaccine, explaining 78% of the variance (adjusted R squared = 0.78). Men (OR = 4.35, 95% CI 1.58–11.93), educated respondents (OR = 3.54, 95% CI 1.44–8.67) and respondents who had received the seasonal influenza vaccine in the previous year (OR = 3.31, 95% CI 1.22–9.00) stated higher intention to receive COVID-19 vaccine. Participants were more likely to be willing to get vaccinated if they reported higher levels of perceived benefits of COVID-19 vaccine (OR = 4.49, 95% CI 2.79–7.22), of perceived severity of COVID-19 infection (OR = 2.36, 95% CI 1.58–3.51) and of cues to action (OR = 1.99, 95% CI 1.38–2.87), according to HBM, and if they reported higher levels of subjective norms (OR = 3.04, 95% CI 2.15–4.30) and self-efficacy (OR = 2.05, 95% CI 1.54–2.72) according to TPB. Although half of the respondents reported they had not received influenza vaccine last year, 40% of them intended to receive influenza vaccine in the coming winter and 66% of them intended to receive COVID-19 vaccine. Providing data on the public perspective and predicting intention for COVID-19 vaccination using HBM and TPB is important for health policy makers and healthcare providers and can help better guide compliance as the COVID-19 vaccine becomes available to the public.

Expansion sequencing: Spatially precise in situ transcriptomics in intact biological systems.

Abstract: Methods for highly multiplexed RNA imaging are limited in spatial resolution and thus in their ability to localize transcripts to nanoscale and subcellular compartments. We adapt expansion microscopy, which physically expands biological specimens, for long-read untargeted and targeted in situ RNA sequencing. We applied untargeted expansion sequencing (ExSeq) to the mouse brain, which yielded the readout of thousands of genes, including splice variants. Targeted ExSeq yielded nanoscale-resolution maps of RNAs throughout dendrites and spines in the neurons of the mouse hippocampus, revealing patterns across multiple cell types, layer-specific cell types across the mouse visual cortex, and the organization and position-dependent states of tumor and immune cells in a human metastatic breast cancer biopsy. Thus, ExSeq enables highly multiplexed mapping of RNAs from nanoscale to system scale.

Upper limits on the isotropic gravitational-wave background from Advanced LIGO and Advanced Virgo’s third observing run

Abstract: We report results of a search for an isotropic gravitational-wave background (GWB) using data from Advanced LIGO’s and Advanced Virgo’s third observing run (O3) combined with upper limits from the earlier O1 and O2 runs. Unlike in previous observing runs in the advanced detector era, we include Virgo in the search for the GWB. The results of the search are consistent with uncorrelated noise, and therefore we place upper limits on the strength of the GWB. We find that the dimensionless energy density Ω GW ≤ 5.8 × 10 − 9 at the 95% credible level for a flat (frequency-independent) GWB, using a prior which is uniform in the log of the strength of the GWB, with 99% of the sensitivity coming from the band 20–76.6 Hz; Ω GW ( f ) ≤ 3.4 × 10 − 9 at 25 Hz for a power-law GWB with a spectral index of 2 / 3 (consistent with expectations for compact binary coalescences), in the band 20–90.6 Hz; and Ω GW ( f ) ≤ 3.9 × 10 − 10 at 25 Hz for a spectral index of 3, in the band 20–291.6 Hz. These upper limits improve over our previous results by a factor of 6.0 for a flat GWB, 8.8 for a spectral index of 2 / 3 , and 13.1 for a spectral index of 3. We also search for a GWB arising from scalar and vector modes, which are predicted by alternative theories of gravity; we do not find evidence of these, and place upper limits on the strength of GWBs with these polarizations. We demonstrate that there is no evidence of correlated noise of magnetic origin by performing a Bayesian analysis that allows for the presence of both a GWB and an effective magnetic background arising from geophysical Schumann resonances. We compare our upper limits to a fiducial model for the GWB from the merger of compact binaries, updating the model to use the most recent data-driven population inference from the systems detected during O3a. Finally, we combine our results with observations of individual mergers and show that, at design sensitivity, this joint approach may yield stronger constraints on the merger rate of binary black holes at z ≳ 2 than can be achieved with individually resolved mergers alone.

Measurement and entanglement phase transitions in all-to-all quantum circuits, on quantum trees, and in Landau-Ginsburg theory

Abstract: A quantum many-body system whose dynamics includes local measurements at a nonzero rate can be in distinct dynamical phases, with differing entanglement properties We introduce theoretical approaches to measurement-induced phase transitions (MPTs) and also to entanglement transitions in random tensor networks Many of our results are for “all-to-all” quantum circuits with unitaries and measurements, in which any qubit can couple to any other, and related settings where some of the complications of low-dimensional models are reduced We also propose field-theory descriptions for spatially local systems of any finite dimensionality To build intuition, we first solve the simplest “minimal cut” toy model for entanglement dynamics in all-to-all circuits, finding scaling forms and exponents within this approximation We then show that certain all-to-all measurement circuits allow exact results by exploiting local treelike structure in the circuit geometry For this reason, we make a detour to give general universal results for entanglement phase transitions in a class of random tree tensor networks with bond dimension 2, making a connection with the classical theory of directed polymers on a tree We then compare these results with numerics in all-to-all circuits, both for the MPT and for the simpler “forced-measurement phase transition” (FMPT) We characterize the two different phases in all-to-all circuits using observables that are sensitive to the amount of information that is propagated between the initial and final time We demonstrate signatures of the two phases that can be understood from simple models Finally we propose Landau-Ginsburg-Wilson-like field theories for the measurement phase transition, the forced-measurement phase transition, and for entanglement transitions in random tensor networks This analysis shows a surprising difference between the measurement phase transition and the other cases We discuss variants of the measurement problem with additional structure (for example free-fermion structure), and questions for the future

Potential Antigenic Cross-reactivity Between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Dengue Viruses.

Abstract: BACKGROUND: Coronavirus disease 2019 (COVID-19) and dengue fever are difficult to distinguish given shared clinical and laboratory features. Failing to consider COVID-19 due to false-positive dengue serology can have serious implications. We aimed to assess this possible cross-reactivity. METHODS: We analyzed clinical data and serum samples from 55 individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To assess dengue serology status, we used dengue-specific antibodies by means of lateral-flow rapid test, as well as enzyme-linked immunosorbent assay (ELISA). Additionally, we tested SARS-CoV-2 serology status in patients with dengue and performed in-silico protein structural analysis to identify epitope similarities. RESULTS: Using the dengue lateral-flow rapid test we detected 12 positive cases out of the 55 (21.8%) COVID-19 patients versus zero positive cases in a control group of 70 healthy individuals (P = 2.5E-5). This includes 9 cases of positive immunoglobulin M (IgM), 2 cases of positive immunoglobulin G (IgG), and 1 case of positive IgM as well as IgG antibodies. ELISA testing for dengue was positive in 2 additional subjects using envelope protein directed antibodies. Out of 95 samples obtained from patients diagnosed with dengue before September 2019, SARS-CoV-2 serology targeting the S protein was positive/equivocal in 21 (22%) (16 IgA, 5 IgG) versus 4 positives/equivocal in 102 controls (4%) (P = 1.6E-4). Subsequent in-silico analysis revealed possible similarities between SARS-CoV-2 epitopes in the HR2 domain of the spike protein and the dengue envelope protein. CONCLUSIONS: Our findings support possible cross-reactivity between dengue virus and SARS-CoV-2, which can lead to false-positive dengue serology among COVID-19 patients and vice versa. This can have serious consequences for both patient care and public health.

3D printing for polymer/particle-based processing: A review

Abstract: The 3D printing method, alternatively known as additive manufacturing (AM), is promising for rapid tooling and layered micromanufacturing. However, significant fundamental research and applied study in the 3D printing area are still necessary to develop new manufacturing mechanisms for combining multi-materials for multiscale and multi-functionality behaviors. Among those materials, particles with unique mechanical, thermal, electrical, optical, and other functional properties can find broad applications in structural composites, thermal packaging, electrical devices, optoelectronics, biomedical implants, energy storage, filtration, and purification. This review will first briefly cover the 3D printing basics before presenting the critical factors in polymer/particle-based printing. We will then introduce a spectrum of different printing mechanisms, i.e., vat polymerization-based, jetting-based, material extrusion-based, powder bed fusion-based, and a few other less utilized 3D printing methods, with a summary of the processing parameters, advantages, disadvantages, and future challenges of each printing technique. During this discussion of 3D printing, we will also present generally used polymers and particles, namely, liquid monomers, viscous inks, compliant gels, stiff filaments, and loosely packed pellets containing micro and nanoscale particles. The emphasis of this review is on the general printing mechanisms applicable in particle- and polymer-relevant processing. To end, this review identifies provides future perspectives regarding some new application examples. Identifying challenges in materials science and manufacturing processes will give direction to the fabrication of multifunctional systems for diverse applications, especially when using multi-materials (e.g., polymers and particles) at multiple scales (e.g., nanoscale morphologies and macroscale structures) for multifunctional systems.

Formalizing Trust in Artificial Intelligence: Prerequisites, Causes and Goals of Human Trust in AI

Abstract: Trust is a central component of the interaction between people and AI, in that 'incorrect' levels of trust may cause misuse, abuse or disuse of the technology. But what, precisely, is the nature of trust in AI? What are the prerequisites and goals of the cognitive mechanism of trust, and how can we promote them, or assess whether they are being satisfied in a given interaction? This work aims to answer these questions. We discuss a model of trust inspired by, but not identical to, interpersonal trust (i.e., trust between people) as defined by sociologists. This model rests on two key properties: the vulnerability of the user; and the ability to anticipate the impact of the AI model's decisions. We incorporate a formalization of 'contractual trust', such that trust between a user and an AI model is trust that some implicit or explicit contract will hold, and a formalization of 'trustworthiness' (that detaches from the notion of trustworthiness in sociology), and with it concepts of 'warranted' and 'unwarranted' trust. We present the possible causes of warranted trust as intrinsic reasoning and extrinsic behavior, and discuss how to design trustworthy AI, how to evaluate whether trust has manifested, and whether it is warranted. Finally, we elucidate the connection between trust and XAI using our formalization.

Reporting guidelines for human microbiome research: the STORMS checklist

Abstract: The particularly interdisciplinary nature of human microbiome research makes the organization and reporting of results spanning epidemiology, biology, bioinformatics, translational medicine and statistics a challenge. Commonly used reporting guidelines for observational or genetic epidemiology studies lack key features specific to microbiome studies. Therefore, a multidisciplinary group of microbiome epidemiology researchers adapted guidelines for observational and genetic studies to culture-independent human microbiome studies, and also developed new reporting elements for laboratory, bioinformatics and statistical analyses tailored to microbiome studies. The resulting tool, called 'Strengthening The Organization and Reporting of Microbiome Studies' (STORMS), is composed of a 17-item checklist organized into six sections that correspond to the typical sections of a scientific publication, presented as an editable table for inclusion in supplementary materials. The STORMS checklist provides guidance for concise and complete reporting of microbiome studies that will facilitate manuscript preparation, peer review, and reader comprehension of publications and comparative analysis of published results.

A wavelength-scale black phosphorus spectrometer

Abstract: On-chip spectrometers with compact footprints are being extensively investigated owing to their promising future in critical applications such as sensing, surveillance and spectral imaging. Most existing miniaturized spectrometers use large arrays of photodetection elements to capture different spectral components of incident light, from which its spectrum is reconstructed. Here, we demonstrate a mid-infrared spectrometer in the 2–9 µm spectral range, utilizing a single tunable black phosphorus photodetector with an active area footprint of only 9 × 16 µm2, along with a unique spectral learning procedure. Such a single-detector spectrometer has a compact size at the scale of the operational wavelength. Leveraging the wavelength and bias-dependent responsivity matrix learned from the spectra of a tunable blackbody source, we reconstruct unknown spectra from their corresponding photoresponse vectors. Enabled by the strong Stark effect and the tunable light–matter interactions in black phosphorus, our single-detector spectrometer shows remarkable potential in the reconstruction of the spectra of both monochromatic and broadband light. Furthermore, its ultracompact structure that is free from bulky interferometers and gratings, together with its electrically reconfigurable nature, may open up pathways towards on-chip mid-infrared spectroscopy and spectral imaging. A single-photodetector spectrometer based on black phosphorus is demonstrated in the wavelength range from 2 to 9 μm. The footprint is 9 × 16 μm2. The spectrometer is free from bulky interferometers and gratings, and is electrically reconfigurable.

HyperSeg: Patch-wise Hypernetwork for Real-time Semantic Segmentation

Abstract: We present a novel, real-time, semantic segmentation network in which the encoder both encodes and generates the parameters (weights) of the decoder. Furthermore, to allow maximal adaptivity, the weights at each decoder block vary spatially. For this purpose, we design a new type of hypernetwork, composed of a nested U-Net for drawing higher level context features, a multi-headed weight generating module which generates the weights of each block in the decoder immediately before they are consumed, for efficient memory utilization, and a primary network that is composed of novel dynamic patch-wise convolutions. Despite the usage of less-conventional blocks, our architecture obtains real-time performance. In terms of the runtime vs. accuracy trade-off, we surpass state of the art (SotA) results on popular semantic segmentation benchmarks: PASCAL VOC 2012 (val. set) and real-time semantic segmentation on Cityscapes, and CamVid. The code is available: https://nirkin.com/hyperseg.

Neonatal antibiotic exposure impairs child growth during the first six years of life by perturbing intestinal microbial colonization.

Abstract: Exposure to antibiotics in the first days of life is thought to affect various physiological aspects of neonatal development. Here, we investigate the long-term impact of antibiotic treatment in the neonatal period and early childhood on child growth in an unselected birth cohort of 12,422 children born at full term. We find significant attenuation of weight and height gain during the first 6 years of life after neonatal antibiotic exposure in boys, but not in girls, after adjusting for potential confounders. In contrast, antibiotic use after the neonatal period but during the first 6 years of life is associated with significantly higher body mass index throughout the study period in both boys and girls. Neonatal antibiotic exposure is associated with significant differences in the gut microbiome, particularly in decreased abundance and diversity of fecal Bifidobacteria until 2 years of age. Finally, we demonstrate that fecal microbiota transplant from antibiotic-exposed children to germ-free male, but not female, mice results in significant growth impairment. Thus, we conclude that neonatal antibiotic exposure is associated with a long-term gut microbiome perturbation and may result in reduced growth in boys during the first six years of life while antibiotic use later in childhood is associated with increased body mass index. In this study, Omry Koren, Samuli Rautava and colleagues report a sex-specific association between neonatal antibiotic exposure and weight and height gain during the first six years of life and showing that boys but not girls exposed to neonatal antibiotics exhibit impaired weight and height development.

Mediated Learning and Cognitive Modifiability

Abstract: This study examines the relation between mediated learning experience (MLE) and cognitive modifiability among children who underwent cultural change. The case of Ethiopian immigrant children who had to adapt to Israeli society, tested by a dynamic assessment (DA) approach, was used. Our main hypothesis, based on L. S. Vygotsky’s (1978) zone of proximal development concept and R. Feuerstein’s (1991) MLE theory, was that these immigrants would reveal cultural difference but not cultural deprivation. A group of first-grade Ethiopian immigrants was compared with a group of Israeli-born children on the Colored Progressive Matrices (CPM), the Children’s Analogical Cognitive Modifiability test, and the Children’s Inferential Thinking Modifiability test. There were significant group differences on the CPM and on the Preteaching scores of both DA measures, indicating superiority of the Israeli-born comparison group. However, after a short but intensive teaching process, the Ethiopian group narrowed the gaps and pe...

DeepFake Detection Based on Discrepancies Between Faces and their Context.

Abstract: We propose a method for detecting face swapping and other identity manipulations in single images. Face swapping methods, such as DeepFake, manipulate the face region, aiming to adjust the face to the appearance of its context, while leaving the context unchanged. We show that this modus operandi produces discrepancies between the two regions (e.g., Fig. 1). These discrepancies offer exploitable telltale signs of manipulation. Our approach involves two networks: (i) a face identification network that considers the face region bounded by a tight semantic segmentation, and (ii) a context recognition network that considers the face context (e.g., hair, ears, neck). We describe a method which uses the recognition signals from our two networks to detect such discrepancies, providing a complementary detection signal that improves conventional real vs. fake classifiers commonly used for detecting fake images. Our method achieves state of the art results on the FaceForensics++, Celeb-DF-v2, and DFDC benchmarks for face manipulation detection, and even generalizes to detect fakes produced by unseen methods.