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  • Open Access English
    Authors: 
    Ariel Israel; Yotam Shenhar; Ilan Green; Eugene Merzon; Avivit Golan-Cohen; Alejandro A. Schäffer; Eytan Ruppin; Shlomo Vinker; Eli Magen;
    Publisher: MDPI

    AbstractBackgroundImmune protection following either vaccination or infection with SARS-CoV-2 decreases over time.ObjectiveTo determine the kinetics of SARS-CoV-2 IgG antibodies following administration of two doses of BNT162b2 vaccine, or SARS-CoV-2 infection in unvaccinated individuals.MethodsAntibody titers were measured between January 31, 2021, and July 31, 2021 in two mutually exclusive groups: i) vaccinated individuals who received two doses of BNT162b2 vaccine and had no history of previous infection with COVID-19 and ii) SARS-CoV-2 convalescents who had not received the vaccine.ResultsA total of 2,653 individuals fully vaccinated by two doses of vaccine during the study period and 4,361 convalescent patients were included. Higher SARS-CoV-2 IgG antibody titers were observed in vaccinated individuals (median 1581 AU/mL IQR [533.8-5644.6]) after the second vaccination, than in convalescent individuals (median 355.3 AU/mL IQR [141.2-998.7]; p<0.001). In vaccinated subjects, antibody titers decreased by up to 40% each subsequent month while in convalescents they decreased by less than 5% per month. Six months after BNT162b2 vaccination 16.1% subjects had antibody levels below the seropositivity threshold of <50 AU/mL, while only 10.8% of convalescent patients were below <50 AU/mL threshold after 9 months from SARS-CoV-2 infection.ConclusionsThis study demonstrates individuals who received the Pfizer-BioNTech mRNA vaccine have different kinetics of antibody levels compared to patients who had been infected with the SARS-CoV-2 virus, with higher initial levels but a much faster exponential decrease in the first group.FundingThis research was internally funded by Leumit Health Services (LHS) and was supported in part by the Intramural Research Program, National Institutes of Health, National Cancer Institute, Center for Cancer Research.The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.Impact statementLarge scale study display the kinetics of SARS-CoV-2 IgG antibodies present in individuals vaccinated with two doses of mRNA vaccine vs. unvaccinated patients who had recovered from the disease: initial levels of antibody are much higher in vaccinated patients, but decrease faster.

  • Open Access English
    Authors: 
    Claire G. Salter; Yiying Cai; Bernice Lo; Guy Helman; Henry Taylor; Amber J. McCartney; Joseph S Leslie; Andrea Accogoli; Frederico Zara; M. Traverso; +35 more
    Countries: Germany, United States, Netherlands, Netherlands

    Abstract Phosphatidylinositol 4-kinase IIIα (PI4KIIIα/PI4KA/OMIM:600286) is a lipid kinase generating phosphatidylinositol 4-phosphate (PI4P), a membrane phospholipid with critical roles in the physiology of multiple cell types. PI4KIIIα’s role in PI4P generation requires its assembly into a heterotetrameric complex with EFR3, TTC7 and FAM126. Sequence alterations in two of these molecular partners, TTC7 (encoded by TTC7A or TCC7B) and FAM126, have been associated with a heterogeneous group of either neurological (FAM126A) or intestinal and immunological (TTC7A) conditions. Here we show that biallelic PI4KA sequence alterations in humans are associated with neurological disease, in particular hypomyelinating leukodystrophy. In addition, affected individuals may present with inflammatory bowel disease, multiple intestinal atresia and combined immunodeficiency. Our cellular, biochemical and structural modelling studies indicate that PI4KA-associated phenotypical outcomes probably stem from impairment of PI4KIIIα-TTC7-FAM126's organ-specific functions, due to defective catalytic activity or altered intra-complex functional interactions. Together, these data define PI4KA gene alteration as a cause of a variable phenotypical spectrum and provide fundamental new insight into the combinatorial biology of the PI4KIIIα-FAM126-TTC7-EFR3 molecular complex. Salter et al. show that biallelic variants in PI4KA—which encodes the enzymatic core of the PI4KIIIα-TTC7-FAM126 complex—cause a clinically diverse disorder comprising neurological, intestinal and immunological abnormalities.

  • Open Access English
    Authors: 
    Ayelet Gertsovski; Merav Ahissar;
    Publisher: Society for Neuroscience
    Project: EC | NeuroCompSkill (833694)

    A main characteristic of dyslexia is poor use of sound categories. We now studied within-session learning of new sound categories in dyslexia, behaviorally and neurally, using fMRI. Human participants (males and females) with and without dyslexia were asked to discriminate which of two serially-presented tones had a higher pitch. The task was administered in two protocols, with and without a repeated reference frequency. The reference condition introduces regularity, and enhances frequency sensitivity in typically developing (TD) individuals. Enhanced sensitivity facilitates the formation of “high” and “low” pitch categories above and below this reference, respectively. We found that in TDs, learning was paralleled by a gradual decrease in activation of the primary auditory cortex (PAC), and reduced activation of the superior temporal gyrus (STG) and left posterior parietal cortex (PPC), which are important for using sensory history. No such sensitivity was found among individuals with dyslexia (IDDs). Rather, IDDs showed reduced behavioral learning of stimulus regularities and no regularity-associated adaptation in the auditory cortex or in higher-level regions. We propose that IDDs' reduced cortical adaptation, associated with reduced behavioral learning of sound regularities, underlies their impoverished use of stimulus history, and consequently impedes their formation of rich sound categories. SIGNIFICANCE STATEMENT Reading difficulties in dyslexia are often attributed to poor use of phonological categories. To test whether poor category use could result from poor learning of new sound categories in general, we administered an auditory discrimination task that examined the learning of new pitch categories above and below a repeated reference sound. Individuals with dyslexia (IDDs) learned categories slower than typically developing (TD) individuals. TD individuals showed adaptation to the repeated sounds that paralleled the category learning in their primary auditory cortex (PAC) and other higher-level regions. In dyslexia, no brain region showed such adaptation. We suggest that poor learning of sound statistics in sensory regions may underlie the poor representations of both speech and nonspeech categories in dyslexia.

  • Publication . Article . Presentation . Conference object . Other literature type . Preprint . 2021
    Open Access English

    We investigate the special case of diamond relay comprising a Gaussian channel with identical frequency response from the user to the relays and fronthaul links with limited rate from the relays to the destination. We use the oblivious compress and forward (CF) with distributed compression and decode and forward (DF) where each relay decodes the whole message and sends half of its bits to the destination. We derive achievable rate by using time-sharing between DF and CF. It is proved that optimal CF-DF time sharing is advantageous over superposition of CF and DF. The optimal time sharing proportion between DF and CF and power and rate allocations are different at each frequency and are fully determined.

  • Open Access English
    Authors: 
    Shelly Meron; Yulia Shenberger; Sharon Ruthstein;
    Publisher: MDPI AG
    Project: EC | CuHypMECH (754365), EC | CuHypMECH (754365)

    Electron paramagnetic resonance (EPR) spectroscopy has emerged as an ideal biophysical tool to study complex biological processes. EPR spectroscopy can follow minor conformational changes in various proteins as a function of ligand or protein binding or interactions with high resolution and sensitivity. Resolving cellular mechanisms, involving small ligand binding or metal ion transfer, is not trivial and cannot be studied using conventional biophysical tools. In recent years, our group has been using EPR spectroscopy to study the mechanism underlying copper ion transfer in eukaryotic and prokaryotic systems. This mini-review focuses on our achievements following copper metal coordination in the diamagnetic oxidation state, Cu(I), between biomolecules. We discuss the conformational changes induced in proteins upon Cu(I) binding, as well as the conformational changes induced in two proteins involved in Cu(I) transfer. We also consider how EPR spectroscopy, together with other biophysical and computational tools, can identify the Cu(I)-binding sites. This work describes the advantages of EPR spectroscopy for studying biological processes that involve small ligand binding and transfer between intracellular proteins.

  • Publication . Article . Preprint . 2021
    Open Access English
    Authors: 
    Dmitry Novikov; Boris Shapiro; Guillaume Tahar;
    Project: EC | EffectiveTG (802107)

    Meromorphic connections on Riemann surfaces originate and are closely related to the classical theory of linear ordinary differential equations with meromorphic coefficients. Limiting behaviour of geodesics of such connections has been studied by e.g. Abate, Bianchi and Tovena in relation with generalized Poincar\'{e}-Bendixson theorems. At present, it seems still to be unknown whether some of the theoretically possible asymptotic behaviours of such geodesics really exist. In order to fill the gap, we use the branched affine structure induced by a Fuchsian meromorphic connection to present several examples with geodesics having infinitely many self-intersections and quite peculiar omega-limit sets. Comment: 15 pages, 4 figures

  • Publication . Article . Preprint . 2021
    Open Access English
    Authors: 
    Ellis, David; Benjamini, Itai;
    Country: United Kingdom

    We continue the study of the properties of graphs in which the ball of radius $r$ around each vertex induces a graph isomorphic to the ball of radius $r$ in some fixed vertex-transitive graph $F$, for various choices of $F$ and $r$. This is a natural extension of the study of regular graphs. More precisely, if $F$ is a vertex-transitive graph and $r \in \mathbb{N}$, we say a graph $G$ is {\em $r$-locally $F$} if the ball of radius $r$ around each vertex of $G$ induces a graph isomorphic to the graph induced by the ball of radius $r$ around any vertex of $F$. We consider the following random graph model: for each $n \in \mathbb{N}$, we let $G_n = G_n(F,r)$ be a graph chosen uniformly at random from the set of all unlabelled, $n$-vertex graphs that are $r$-locally $F$. We investigate the properties possessed by the random graph $G_n$ with high probability, for various natural choices of $F$ and $r$. We prove that if $F$ is a Cayley graph of a torsion-free group of polynomial growth, and $r$ is sufficiently large depending on $F$, then the random graph $G_n = G_n(F,r)$ has largest component of order at most $n^{5/6}$ with high probability, and has at least $\exp(n^{\delta})$ automorphisms with high probability, where $\delta>0$ depends upon $F$ alone. Both properties are in stark contrast to random $d$-regular graphs, which correspond to the case where $F$ is the infinite $d$-regular tree. We also show that, under the same hypotheses, the number of unlabelled, $n$-vertex graphs that are $r$-locally $F$ grows like a stretched exponential in $n$, again in contrast with $d$-regular graphs. In the case where $F$ is the standard Cayley graph of $\mathbb{Z}^d$, we obtain a much more precise enumeration result, and more precise results on the properties of the random graph $G_n(F,r)$. Our proofs use a mixture of results and techniques from geometry, group theory and combinatorics. Comment: Full proof of Theorem 7 added. Statement of Proposition 38 has been strengthened slightly. 61 pages

  • Open Access English
    Authors: 
    Homa Nikbakht; Michele Wigger; Shlomo Shamai;
    Project: EC | CloudRadioNet (694630), EC | CTO Com (715111), EC | CloudRadioNet (694630), EC | CTO Com (715111)

    This paper analyzes the multiplexing gains (MG) for simultaneous transmission of delay-sensitive and delay-tolerant data over interference networks. In the considered model, only delay-tolerant data can profit from coordinated multipoint (CoMP) transmission or reception techniques, because delay-sensitive data has to be transmitted without further delay. Transmission of delay-tolerant data is also subject to a delay constraint, which is however less stringent than the one on delay-sensitive data. Different coding schemes are proposed, and the corresponding MG pairs for delay-sensitive and delay-tolerant data are characterized for Wyner's linear symmetric network and for Wyner's two-dimensional hexagonal network with and without sectorization. For Wyner's linear symmetric also an information-theoretic converse is established and shown to be exact whenever the cooperation rates are sufficiently large or the delay-sensitive MG is small or moderate. These results show that on Wyner's symmetric linear network and for sufficiently large cooperation rates, the largest MG for delay-sensitive data can be achieved without penalizing the maximum sum-MG of both delay-sensitive and delay-tolerant data. A similar conclusion holds for Wyner's hexagonal network only for the model with sectorization. In the model without sectorization, a penalty in sum-MG is incurred whenever one insists on a positive delay-sensitive MG. 41 pages, submitted to Transactions on Communications

  • Open Access English
    Authors: 
    André O. Werneck; Miguel Peralta; Riki Tesler; Adilson Marques;
    Publisher: Elsevier
    Country: Portugal

    Objectives: To investigate the cross-sectional and prospective associations of lifestyle risk behaviors clustering with elevated depressive symptoms and to explore synergic prospective associations of different combinations of lifestyle risk behaviors with subsequent depressive symptoms. Study design: Prospective cohort study. Data on 31,190 middle-aged and older adults from waves 4 (2011) and 6 (2015) of the Survey of Health, Ageing and Retirement in Europe (SHARE) were used. Main outcome measures: Elevated depressive symptoms were estimated using the EURO-D 12-item scale. Lifestyle risk behaviors composing the cluster included physical inactivity, inadequate consumption of fruit and/or vegetables, binge drinking, and tobacco smoking. Gender, age group, education, place of residence, country, number of chronic diseases and body mass index were considered as confounders. Results: With the exception of binge drinking, all lifestyle risk behaviors were associated with higher odds of elevated depressive symptoms in cross-sectional and prospective analyses. The clustering of unhealthy lifestyle behaviors was cross-sectionally associated with elevated depressive symptoms and the clustering of two [odds ratio [OR]: 1.39; 95%CI: 1.28-1.51) and three or four (OR: 1.60; 95%CI: 1.38-1.85) were prospectively associated with elevated depressive symptoms. There were no interactions between the pairs of behaviors in the association with later elevated depressive symptoms. Conclusions: Our findings support the need for interventions integrating multiple health behaviors to prevent elevated depressive symptoms among middle-aged and older adults. This paper uses data from SHARE Waves 4, and 6 (DOIs: 10.6103/SHARE.w4.710 and 10.6103/SHARE.w6.710), see Börsch-Supan et al. (2013) for methodological details. The SHARE data collection has been funded by the European Commission, DG RTD through FP5 (QLK6-CT-2001-00360), FP6 (SHARE-I3: RII-CT-2006-062193, COMPARE: CIT5-CT-2005-028857, SHARELIFE: CIT4-CT-2006-028812), FP7 (SHARE-PREP: GA N°211909, SHARE-LEAP: GA N°227822, SHARE M4: GA N°261982, DASISH: GA N°283646) and Horizon 2020 (SHARE-DEV3: GA N°676536, SHARE-COHESION: GA N°870628, SERISS: GA N°654221, SSHOC: GA N°823782) and by DG Employment, Social Affairs & Inclusion through VS 2015/0195, VS 2016/0135, VS 2018/0285, VS 2019/0332, and VS 2020/0313. Additional funding from the German Ministry of Education and Research, the Max Planck Society for the Advancement of Science, the U.S. National Institute on Aging (U01_AG09740-13S2, P01_AG005842, P01_AG08291, P30_AG12815, R21_AG025169, Y1-AG-4553-01, IAG_BSR06-11, OGHA_04-064, HHSN271201300071C, RAG052527A) and from various national funding sources is gratefully acknowledged (see www.share-project.org). © 2021 Elsevier B.V. All rights reserved.

  • Publication . Article . Preprint . 2021
    Open Access English
    Authors: 
    Andrea Guerrieri; Amit Sever;

    We consider a dual $S$-matrix Bootstrap approach in $d\geq 3$ space-time dimensions which relies solely on the rigorously proven analyticity, crossing, and unitarity properties of the scattering amplitudes. As a proof of principle, we provide rigorous upper and lower numerical bounds on the quartic coupling for the scattering of identical scalar particles in four dimensions. 5 + 10 pages, 3 + 6 figures, major revision in the appendices, improved numerics, typos corrected

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