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Tel Aviv, Israel

Tel Aviv University is a public university located in Ramat Aviv, Tel Aviv, Israel. With over 30,000 students, TAU is Israel's largest university.Located in Israel's cultural, financial and technological core, Tel Aviv University is a major center of teaching and research, comprising 9 faculties, 27 schools, 98 departments and nearly 130 research institutes and centers. Wikipedia.


Lamy D.F.,Tel Aviv University
Journal of vision | Year: 2013

According to most models of selective visual attention, our goals at any given moment and saliency in the visual field determine attentional priority. But selection is not carried out in isolation--we typically track objects through space and time. This is not well captured within the distinction between goal-directed and saliency-based attentional guidance. Recent studies have shown that selection is strongly facilitated when the characteristics of the objects to be attended and of those to be ignored remain constant between consecutive selections. These studies have generated the proposal that goal-directed or top-down effects are best understood as intertrial priming effects. Here, we provide a detailed overview and critical appraisal of the arguments, experimental strategies, and findings that have been used to promote this idea, along with a review of studies providing potential counterarguments. We divide this review according to different types of attentional control settings that observers are thought to adopt during visual search: feature-based settings, dimension-based settings, and singleton detection mode. We conclude that priming accounts for considerable portions of effects attributed to top-down guidance, but that top-down guidance can be independent of intertrial priming.


Sakaguchi H.,Kyushu University | Malomed B.A.,Tel Aviv University
Optics Letters | Year: 2012

We demonstrate that modulation of the local strength of the cubic self-focusing (SF) nonlinearity in the twodimensional geometry, in the form of a circle with contrast Δg of the SF coefficient relative to the ambient medium with a weaker nonlinearity, stabilizes a family of fundamental solitons against the critical collapse. The result is obtained in an analytical form, using the variational approximation and Vakhitov-Kolokolov stability criterion, and corroborated by numerical computations. For the small contrast, the stability interval of the soliton's norm scales as ΔN ∼ Δg (the replacement of the circle by an annulus leads to a reduction of the stability region by perturbations breaking the axial symmetry). To further illustrate this mechanism, we demonstrate, in an exact form, the stabilization of one-dimensional solitons against the critical collapse under the action of a locally enhanced quintic SF nonlinearity. © 2012 Optical Society of America.


Brodsky S.J.,SLAC | De Teramond G.,University of Costa Rica | Karliner M.,Tel Aviv University
Annual Review of Nuclear and Particle Science | Year: 2012

We review some outstanding puzzles and experimental anomalies in hadron physics that appear to challenge conventional wisdom and, in some cases, the foundations of quantum chromodynamics (QCD). We also discuss possible solutions and propose new tests and experiments that could illuminate the underlying physics and novel phenomenological features of QCD. In some cases, new perspectives for QCD physics have emerged. © 2012 by Annual Reviews.


Esteves A.R.,University of Coimbra | Gozes I.,Tel Aviv University | Cardoso S.M.,University of Coimbra
Biochimica et Biophysica Acta - Molecular Basis of Disease | Year: 2014

In Parkinson's disease mitochondrial dysfunction can lead to a deficient ATP supply to microtubule protein motors leading to mitochondrial axonal transport disruption. Compromised axonal transport will then lead to a disorganized distribution of mitochondria and other organelles in the cell, as well as, the accumulation of aggregated proteins like alpha-synuclein. Moreover, axonal transport disruption can trigger synaptic accumulation of autophagosomes packed with damaged mitochondria and protein aggregates promoting synaptic failure.We previously observed that neuronal-like cells with an inherent mitochondrial impairment derived from PD patients contain a disorganized microtubule network, as well as, alpha-synuclein oligomer accumulation. In this work we provide new evidence that an agent that promotes microtubule network assembly, NAP (davunetide), improves microtubule-dependent traffic, restores the autophagic flux and potentiates autophagosome-lysosome fusion leading to autophagic vacuole clearance in Parkinson's disease cells. Moreover, NAP is capable of efficiently reducing alpha-synuclein oligomer content and its sequestration by the mitochondria. Most interestingly, NAP decreases mitochondrial ubiquitination levels, as well as, increases mitochondrial membrane potential indicating a rescue in mitochondrial function.Overall, we demonstrate that by improving microtubule-mediated traffic, we can avoid mitochondrial-induced damage and thus recover cell homeostasis. These results prove that NAP may be a promising therapeutic lead candidate for neurodegenerative diseases that involve axonal transport failure and mitochondrial impairment as hallmarks, like Parkinson's disease and related disorders. © 2013 Elsevier B.V.


Schwartzman O.,Tel Aviv University | Schwartzman O.,Functional Genomics and Childhood Leukemia Research Section | Schwartzman O.,Weizmann Institute of Science | Tanay A.,Weizmann Institute of Science
Nature Reviews Genetics | Year: 2015

Epigenomics is the study of the physical modifications, associations and conformations of genomic DNA sequences, with the aim of linking these with epigenetic memory, cellular identity and tissue-specific functions. While current techniques in the field are characterizing the average epigenomic features across large cell ensembles, the increasing interest in the epigenetics within complex and heterogeneous tissues is driving the development of single-cell epigenomics. We review emerging single-cell methods for capturing DNA methylation, chromatin accessibility, histone modifications, chromosome conformation and replication dynamics. Together, these techniques are rapidly becoming a powerful tool in studies of cellular plasticity and diversity, as seen in stem cells and cancer. © 2015 Macmillan Publishers Limited.


Piro A.L.,California Institute of Technology | Nakar E.,Tel Aviv University
Astrophysical Journal | Year: 2014

Ongoing transient surveys are presenting an unprecedented account of the rising light curves of Type Ia supernovae (SNe Ia). This early emission probes the shallowest layers of the exploding white dwarf (WD), which can provide constraints on the progenitor star and the properties of the explosive burning. We use semianalytic models of radioactively powered rising light curves to analyze these observations. As we have summarized in previous work, the main limiting factor in determining the surface distribution of 56Ni is the lack of an unambiguously identified time of explosion, as would be provided by detection of shock breakout or shock-heated cooling. Without this the SN may in principle exhibit a "dark phase" for a few hours to days, where the only emission is from shock-heated cooling that is too dim to be detected. We show that by assuming a theoretically motivated time-dependent velocity evolution, the explosion time can be better constrained, albeit with potential systematic uncertainties. This technique is used to infer the surface 56Ni distributions of three recent SNe Ia that were caught especially early in their rise. In all three we find fairly similar 56Ni distributions. Observations of SN 2011fe and SN 2012cg probe shallower depths than SN 2009ig, and in these two cases 56Ni is present merely 10 -2 M from the WDs' surfaces. The uncertainty in this result is up to an order of magnitude given the difficulty of precisely constraining the explosion time. We also use our conclusions about the explosion times to reassess radius constraints for the progenitor of SN 2011fe, as well as discuss the roughly t2 power law that is inferred for many observed rising light curves. © 2014. The American Astronomical Society. All rights reserved..


Bitansky N.,Tel Aviv University | Paneth O.,Boston University
Proceedings - Annual IEEE Symposium on Foundations of Computer Science, FOCS | Year: 2012

The introduction of a non-black-box simulation technique by Barak (FOCS 2001) has been a major landmark in cryptography, breaking the previous barriers of black-box impossibility. Barak's techniques were subsequently extended and have given rise to various powerful applications. We present the first non-black-box simulation technique that does not rely on Barak's technique (or on non-standard assumptions). Our technique is based on essentially different tools: it does not invoke universal arguments}, nor does it rely on collision-resistant hashing. Instead, the main ingredient we use is the impossibility of general program obfuscation (Barak et al., CRYPTO 2001). Using our technique, we construct a new resettably-sound zero-knowledge (rsZK) protocol. rsZK protocols remain sound even against cheating provers that can repeatedly reset the verifier to its initial state and random tape. Indeed, for such protocols black-box simulation is impossible. Our rsZK protocol is the first to be based solely on semi-honest oblivious transfer and does not rely on collision-resistant hashing, in addition, our protocol does not use PCP machinery. In the converse direction, we show a generic transformation from any rsZK protocol to a family of functions that cannot be obfuscated. © 2012 IEEE.


Seguro L.P.C.,University of Sao Paulo | Rosario C.,Hospital de Pedro Hispano | Shoenfeld Y.,Tel Aviv University
Autoimmunity Reviews | Year: 2013

Glucocorticoids (GC) are essential in the management of several medical conditions but its long-term use is associated with complications in diverse organs and systems. The aim of the present study is to review the long-term complications of past GC use.Permanent damage related to GC can affect patient's life even years after its withdrawal. Classical examples are cataracts and esthetic problems like skin atrophy, striae, acne and obesity. Interestingly, for some complications, the risk of an incident event can persist for past GC use. Higher risks of osteoporosis, osteonecrosis, cardiovascular disease, infections and cancer have been associated with prior GC therapy. These evidences reinforce the importance of limiting our GC prescriptions at its lower possible dose. © 2012 Elsevier B.V.


Gefen A.,Tel Aviv University
Journal of Tissue Viability | Year: 2011

In this study, a mathematical model is developed for analyzing the effects of the microclimate on skin tolerance to superficial pressure ulcers (SPUs). The modeling identified the following factors as such that decrease the tolerance of skin to SPUs: (i) increase in the skin temperature, (ii) increase in the ambient temperature, (iii) increase in the relative humidity, (iv) increase in the skin-support (or skin-clothing-support) contact pressures, and (v) decrease in permeabilities of the materials contacting the skin or being close to it, e.g. the covering sheet of the support and clothing. The modeling is consistent with relevant empirical findings and clinical observations documented in the literature, explains them from a basic science aspect, and can be further developed for design of interventions, safer patient clothing and supports that consider the optimization of microclimate factors. © 2011 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.


Migirov L.,Tel Aviv University
European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery | Year: 2013

Current paper presents a surgical technique and preliminary results of the first eight consecutive fully endoscopic transcanal stapedotomies. All eight procedures were performed under local anesthesia by the same surgeon using rigid endoscopes of 3-mm diameter, 14-cm length, 0° and 30°. A posterior tympanomeatal flap was elevated transmeatally with the 0° endoscope and then transposed anteriorly. Stapes fixation was confirmed, the stapes tendon was cut with curved micro-scissors, and the stapes was separated from the incus in the incudo-stapedial joint. The anterior and posterior stapedial crus were carefully fractured, and the superstructure was removed. The hole in the foot-plate was created with a Skeeter microdrill using a 0.5-mm-diameter diamond burr. A platinum/fluoroplastic piston prosthesis (0.4-mm diameter) was placed into this hole and fitted along the long process of the incus. The tympano-meatal flap was repositioned, and the external auditory canal was filled with Gelfoam(®). The chorda tympani nerve was preserved in all cases. A 4.5-mm prosthesis was used in six cases and a 4.75-mm prosthesis in two. Pure tone audiograms demonstrated improved air- and bone-conduction threshold averages across the three speech frequencies (0.5-1.2 kHz) 6 months after surgery (64 vs. 29.8 dB and 30.6 vs. 25.1 dB, respectively). The average postoperative air-bone gap was within 10 dB in six ears and between 10 and 15 dB in the other two ears. Our preliminary results indicate that transcanal fully endoscopic stapedotomy is a feasible and safe technique for surgical management of hearing loss associated with otosclerosis.


Sadeh A.,Tel Aviv University
Monographs of the Society for Research in Child Development | Year: 2015

Sleep is a complex phenomenon that could be understood and assessed at many levels. Sleep could be described at the behavioral level (relative lack of movements and awareness and responsiveness) and at the brain level (based on EEG activity). Sleep could be characterized by its duration, by its distribution during the 24-hr day period, and by its quality (e.g., consolidated versus fragmented). Different methods have been developed to assess various aspects of sleep. This chapter covers the most established and common methods used to assess sleep in infants and children. These methods include polysomnography, videosomnography, actigraphy, direct observations, sleep diaries, and questionnaires. The advantages and disadvantages of each method are highlighted. © 2015 The Society for Research in Child Development, Inc.


Paul M.,Tel Aviv University
Cochrane database of systematic reviews (Online) | Year: 2010

Several beta-lactams are recommended as single agents for the treatment of febrile neutropenia. To compare the effectiveness of different anti-pseudomonal beta-lactams as single agents in the treatment of febrile neutropenia. To compare the development of bacterial resistance, bacterial and fungal superinfections during or following treatment with the different beta-lactams. We searched the Cochane Register of Controlled Trials (CENTRAL), Issue 3, 2010. MEDLINE, EMBASE, LILACS, FDA drug applications, conference proceedings and ongoing clinical trial databases up to August 2010. References of included studies were scanned. Randomised controlled trials (RCTs) comparing an antipseudomonal beta-lactam to another antipseudomonal beta-lactam antibiotic, both given alone or with the addition of the same glycopeptide to both study arms, for the initial treatment of fever and neutropenia among cancer patients. Two review authors applied inclusion criteria and extracted the data independently. Missing data were sought. Risk ratios (RR) were calculated with 95% confidence intervals (CI), and pooled using the fixed effect model. The primary outcome was all-cause mortality. Risk of bias was assessed using a domain-based evaluation and its effect of results was assessed through sensitivity analyses. Forty-four trials were included. The antibiotics assessed were cefepime, ceftazidime, piperacillin-tazobactam, imipenem and meropenem. Adequate allocation concealment and generation were reported in about half of the trials and only two trials were double-blinded. The risk for all-cause mortality was significantly higher with cefepime compared to other beta-lactams (RR 1.39, 95% CI 1.04 to 1.86, 21 trials, 3471 participants), without heterogeneity and with higher RRs in trials at low risk for bias. There were no differences in secondary outcomes but for a non-significantly higher rate of bacterial superinfections with cefepime. Mortality was significantly lower with piperacillin-tazobactam compared to other antibiotics (RR 0.56, 95% CI 0.34 to 0.92, 8 trials, 1314 participants), without heterogeneity. Carbapenems resulted in similar all-cause mortality and a lower rate of clinical failure and antibiotic modifications as compared to other antibiotics, but a higher rate of diarrhea caused by Clostridium difficile. Current evidence supports the use of piperacillin-tazobactam in locations where antibiotic resistance profiles do not mandate empirical use of carbapenems. Carbapenems result in a higher rate of antibiotic-associated and Clostridium difficile-associated diarrhea. There is a high level of evidence that all-cause mortality is higher with cefepime compared to other beta-lactams and it should not be used as monotherapy for patients with febrile neutropenia.


Shoenfeld Y.,Tel Aviv University
Clinical Reviews in Allergy and Immunology | Year: 2012

There have been enormous strides in our understanding of autoimmunity. These strides have come under the umbrellas of epidemiology, immunological phenotype and function, disease definitions and classification and especially new therapeutic reagents. However, while these advances have been herculean, there remains enormous voids. Some of these voids include genetic susceptibility and the interaction of genes and environment. The voids include induction of tolerance in preclinical disease and definitions of host susceptibility and responses to the expensive biologic agents. The voids include the so-called clustering of human autoimmune diseases and the issues of whether the incidence is rising in our western society. Other voids include the relationships between microbiology, vaccination, gut flora, overzealous use of antibiotics, and the role of nanoparticles and environmental pollution in either the induction or the natural history of disease. One cannot even begin to address even a fraction of these issues. However, in this special issue, we are attempting to discuss clinical issues in autoimmunity that are not usually found in generic reviews. The goal is to bring to the readership provocative articles that ultimately will lead to improvement in patient care. © 2011 Springer Science+Business Media, LLC.


Chai H.,Tel Aviv University
Acta Biomaterialia | Year: 2014

The mechanical properties of tooth enamel generally exhibit large variations, which reflect its structural and material complexity. Some key properties were evaluated under localized contact, simulating actual functioning conditions. Prominent cusps of extracted human molar teeth were polished down ∼0.7 mm below the cusp tip and indented by tungsten carbide balls. The internal damage was assessed after unloading from longitudinal or transverse sections. The ultimate tensile stress (UTS) was determined using a novel bilayer specimen. The damage is characterized by penny-like radial cracks driven by hoop stresses and cylindrical cracks driven along protein-rich interrod materials by shear stresses. Shallow cone cracks typical of homogeneous materials which may cause rapid tooth wear under repeat contact are thus avoided. The mean stress vs. indentation strain curve is highly nonlinear, attributable to plastic shearing of protein between and within enamel rods. This curve is also affected by damage, especially radial cracks, the onset of which depends on ball radius. Several material properties were extracted from the tests, including shear strain at the onset of ring cracks γF (= 0.14), UTS (= 119 MPa), toughness KC (= 0.94 MPa m1/2), a crack propagation law and a constitutive response determined by trial and error with the aid of a finite-element analysis. These quantities, which are only slightly sensitive to anatomical location within the enamel region tested, facilitate a quantitative assessment of crown failure. Causes for variations in published UTS and KC values are discussed. © 2014 Acta Materialia Inc.


Nowak-Wegrzyn A.,Mount Sinai School of Medicine | Katz Y.,Tel Aviv University | Mehr S.S.,Childrens Hospital at Westmead | Koletzko S.,Ludwig Maximilians University of Munich
Journal of Allergy and Clinical Immunology | Year: 2015

Non-IgE-mediated gastrointestinal food-induced allergic disorders (non-IgE-GI-FAs) account for an unknown proportion of food allergies and include food protein-induced enterocolitis syndrome (FPIES), food protein-induced allergic proctocolitis (FPIAP), and food protein-induced enteropathy (FPE). Non-IgE-GI-FAs are separate clinical entities but have many overlapping clinical and histologic features among themselves and with eosinophilic gastroenteropathies. Over the past decade, FPIES has emerged as the most actively studied non-IgE-GI-FA, potentially because of acute and distinct clinical features. FPIAP remains among the common causes of rectal bleeding in infants, while classic infantile FPE is rarely diagnosed. The overall most common allergens are cow's milk and soy; in patients with FPIES, rice and oat are also common. The most prominent clinical features of FPIES are repetitive emesis, pallor, and lethargy; chronic FPIES can lead to failure to thrive. FPIAP manifests with bloody stools in well-appearing young breast-fed or formula-fed infants. Features of FPE are nonbloody diarrhea, malabsorption, protein-losing enteropathy, hypoalbuminemia, and failure to thrive. Non-IgE-GI-FAs have a favorable prognosis; the majority resolve by 1 year in patients with FPIAP, 1 to 3 years in patients with FPE, and 1 to 5 years in patients with FPIES, with significant differences regarding specific foods. There is an urgent need to better define the natural history of FPIES and the pathophysiology of non-IgE-GI-FAs to develop biomarkers and novel therapies. © 2015 American Academy of Allergy, Asthma & Immunology.


Jami E.,Israel Agricultural Research Organization | Jami E.,Tel Aviv University | Mizrahi I.,Israel Agricultural Research Organization
PLoS ONE | Year: 2012

The bovine rumen houses a complex microbiota which is responsible for cattle's remarkable ability to convert indigestible plant mass into food products. Despite this ecosystem's enormous significance for humans, the composition and similarity of bacterial communities across different animals and the possible presence of some bacterial taxa in all animals' rumens have yet to be determined. We characterized the rumen bacterial populations of 16 individual lactating cows using tag amplicon pyrosequencing. Our data showed 51% similarity in bacterial taxa across samples when abundance and occurrence were analyzed using the Bray-Curtis metric. By adding taxon phylogeny to the analysis using a weighted UniFrac metric, the similarity increased to 82%. We also counted 32 genera that are shared by all samples, exhibiting high variability in abundance across samples. Taken together, our results suggest a core microbiome in the bovine rumen. Furthermore, although the bacterial taxa may vary considerably between cow rumens, they appear to be phylogenetically related. This suggests that the functional requirement imposed by the rumen ecological niche selects taxa that potentially share similar genetic features. © 2012 Jami, Mizrahi.


Kupiec M.,Tel Aviv University
FEMS Microbiology Reviews | Year: 2014

Telomeres are nucleoprotein structures that cap the ends of the linear eukaryotic chromosomes and thereby protect their stability and integrity. Telomeres play central roles in maintaining the genome's integrity, distinguishing between the natural chromosomal ends and unwanted double-stranded breaks. In addition, telomeres are replicated by a special reverse transcriptase called telomerase, in a complex mechanism that is coordinated with the genome's replication. Telomeres also play an important role in tethering the chromosomes to the nuclear envelope, thus helping in positioning the chromosomes within the nucleus. The special chromatin configuration of telomeres affects the expression of nearby genes; nonetheless, telomeres are transcribed, creating noncoding RNA molecules that hybridize to the chromosomal ends and seem to play regulatory roles. The yeast Saccharomyces cerevisiae, with its sophisticated genetics and molecular biology, has provided many fundamental concepts in telomere biology, which were later found to be conserved in all organisms. Here, we present an overview of all the aspects of telomere biology investigated in yeast, which continues to provide new insights into this complex and important subject, which has significant medical implications, especially in the fields of aging and cancer. Telomeres, the eukaryotic chromosomal ends, preserve genome stability and help duplicate the genome. They play important roles in aging and cancer. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.


Belmaker J.,Tel Aviv University | Parravicini V.,Institute Of Recherche Pour Le Developpement | Kulbicki M.,Institute Of Recherche Pour Le Developpement
Global Change Biology | Year: 2013

Alien species are considered one of the prime threats to biodiversity, driving major changes in ecosystem structure and function. Identifying the traits associated with alien introduction has been largely restricted to comparing indigenous and alien species or comparing alien species that differ in abundance or impact. However, a more complete understanding may emerge when the entire pool of potential alien species is used as a control, information that is rarely available. In the eastern Mediterranean, the marine environment is undergoing an unparalleled species composition transformation, as a flood of aliens have entered from the Red Sea following the opening of the Suez Canal in 1869. In this study, we compile data on species traits, geographical distribution, and environmental affinity of the entire pool of reef-associated fish species in the Red Sea and more generally across the Indo-Pacific. We use this extensive data to identify the prime characteristics separating Red Sea species that have become alien in the Mediterranean from those that have not. We find that alien species occupy a larger range of environments in their native ranges, explaining their ability to colonize the seasonal Mediterranean. Red Sea species that naturally experience high maximum temperatures in their native range have a high probability of becoming alien. Thus, contrary to predictions of an accelerating number of aliens following increased water temperatures, hotter summers in this region may prevent the establishment of many alien species. We further find that ecological trait diversity of alien species is substantially more evenly spaced and more divergent than random samples from the pool of Red Sea species, pointing at additional processes, such as competition, promoting ecological diversity among alien species. We use these results to provide a first quantitative ranking of the potential of Red Sea species to become established in the eastern Mediterranean. © 2012 Blackwell Publishing Ltd.


Beilis I.I.,Tel Aviv University
IEEE Transactions on Plasma Science | Year: 2011

Time-dependent cathode potential drop (CPD) is studied for a transient cathode spot on a Cu cathode protrusion when the spot operates continuously. A transient heat model was self-consistently developed, taking into account the kinetics of cathode vapor flow in a Knudsen layer, considering the momentum and energy conservation in the sheath, the electron relaxation zone, and the hydrodynamic region of the expanding plasma. The difference between evaporated and return fluxes of heavy particles determines the protrusion erosion rate and, hence, the decrease of its size during transient spot operation. It is shown that the spot parameters (e.g., CPD, temperature, and density) change from an initial to a steady-state value with time. Thus, for continuous spot operation on a Cu protrusion with a 5-μm radius, the CPD is about 90 V when the spot originates from initial plasma with a time duration of less than 50 ns and decreases to 13 V when spot operation continues up to 1 μs. This result explains the relatively large power supply voltage (∼ 100 V) needed for arc ignition (after triggering the initial plasma at the cathode in a low-voltage electrode gap) compared to the low CPD appearing during steady-state arc operation. The calculated potential drop in the plasma expansion region at steady state is about 5 V, and the sum of this value with the CPD agrees well with the measured Cu arc voltage. The spot initiation and development can be consistently described as a vaporization mechanism by the gasdynamic model without involving any phenomena of explosion of irregularities at the cathode surface. © 2011 IEEE.


Hod O.,Tel Aviv University
Physical Review B - Condensed Matter and Materials Physics | Year: 2012

Superlubricity is a frictionless tribological state sometimes occurring in nanoscale material junctions. It is often associated with incommensurate surface lattice structures appearing at the interface. Here, by using the recently introduced registry-index concept that quantifies the registry mismatch in layered materials and reproduces their interlayer sliding energy landscape, we prove the existence of a direct relation between interlayer commensurability and wearless friction in rigid layered materials. We show that our simple and intuitive model is able to capture, down to fine details, the experimentally measured frictional behavior of a hexagonal graphene flake sliding on top of the surface of graphite. We further predict that superlubricity is expected to occur in hexagonal boron nitride as well with tribological characteristics very similar to those observed for the graphitic system. The success of our method in predicting experimental results along with its high computational efficiency marks the registry index as a promising tool for studying tribological properties of nanoscale material interfaces. © 2012 American Physical Society.


Lotem A.,Tel Aviv University | Halpern J.Y.,Cornell University
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2012

A fundamental and frequently overlooked aspect of animal learning is its reliance on compatibility between the learning rules used and the attentional and motivational mechanisms directing them to process the relevant data (called here data-acquisition mechanisms). We propose that this coordinated action, which may first appear fragile and error prone, is in fact extremely powerful, and critical for understanding cognitive evolution. Using basic examples from imprinting and associative learning, we argue that by coevolving to handle the natural distribution of data in the animal's environment, learning and data-acquisition mechanisms are tuned jointly so as to facilitate effective learning using relatively little memory and computation. We then suggest that this coevolutionary process offers a feasible path for the incremental evolution of complex cognitive systems, because it can greatly simplify learning. This is illustrated by considering how animals and humans can use these simple mechanisms to learn complex patterns and represent them in the brain. We conclude with some predictions and suggested directions for experimental and theoretical work. © 2012 The Royal Society.


Aloni R.,Tel Aviv University
Trees - Structure and Function | Year: 2015

Key message: Environmental cues regulate plant vascular differentiation and plant evolution through simple hormonal mechanisms of a single or a few moving signals.Abstract: Mechanisms regulating the responses of plants and their vascular tissues to environmental stimuli are mediated by continuously moving hormonal signals that enable continuous response to ecological cues. Auxin from young leaves is the primary hormonal signal that can induce vascular differentiation by itself. Its concentrations determine whether phloem or xylem is induced. Auxin produced in a parasitic plant induces continuous vessel system into its host with open perforation at their junction. Polar auxin gradients along trees regulate the gradual widening of vessel diameter and decrease in vessel density from leaves to roots. This basic mechanism also regulates vascular adaptation to the plant’s environment. Gibberellin from mature leaves, in the presence of auxin, promotes cambial activity and woodiness, and is the specific signal inducing fibers. The evolutionary development of vessels and fibers from tracheids reflects their hormonal specialization; from the combined mechanism of auxin and gibberellin for tracheids in gymnosperms, to the specialized mechanisms of auxin inducing vessels, and gibberellin inducing fibers in angiosperms. Cytokinin from root tips promotes cambial activity and sensitivity enabling the extreme differentiation of ring-porous wood in temperate deciduous hardwood trees. These mechanisms are discussed for clarifying the role of the environment in vascular adaption and evolution. © 2014, Springer-Verlag Berlin Heidelberg.


Fouxon I.,Tel Aviv University
Physical Review Letters | Year: 2012

The inertia of particles driven by the turbulent flow of the surrounding fluid makes them prefer certain regions of the flow. The heavy particles lag behind the flow and tend to accumulate in the regions with less vorticity, while the light particles do the opposite. As a result of the long-time evolution, the particles distribute over a multifractal attractor in space. We consider this distribution using our recent results on the steady states of chaotic dynamics. We describe the preferential concentration analytically and derive the correlation functions of density and the fractal dimensions of the attractor. The results are obtained for real turbulence and are testable experimentally. © 2012 American Physical Society.


Aigrain S.,University of Oxford | Pont F.,University of Exeter | Zucker S.,Tel Aviv University
Monthly Notices of the Royal Astronomical Society | Year: 2012

We present a new, simple method to predict activity-induced radial velocity (RV) variations using high-precision time series photometry. It is based on insights from a simple spot model, has only two free parameters (one of which can be estimated from the light curve) and does not require knowledge of the stellar rotation period. We test the method on simulated data and illustrate its performance by applying it toMOST/SOPHIE observations of the planet host star HD189733, where it gives almost identical results to much more sophisticated but highly degenerate models, and synthetic data for the Sun, where we demonstrate that it can reproduce variations well below the ms -1 level. We also apply it to quarter 1 data forKeplertransit candidate host stars, where it can be used to estimate RV variations down to the 2-3ms -1 level, and show that RV amplitudes above that level may be expected for approximately two-thirds of the candidates we examined. © 2011 The Authors Monthly Notices of the Royal Astronomical Society © 2011 RAS.


Holcman D.,Ecole Normale Superieure de Paris | Schuss Z.,Tel Aviv University
Reports on Progress in Physics | Year: 2013

Critical biological processes, such as synaptic plasticity and transmission, activation of genes by transcription factors, or double-strained DNA break repair, are controlled by diffusion in structures that have both large and small spatial scales. These may be small binding sites inside or on the surface of the cell, or narrow passages between subcellular compartments. The great disparity in spatial scales is the key to controlling cell function by structure. We report here recent progress on resolving analytical and numerical difficulties in extracting properties from experimental data, from biophysical models, and from Brownian dynamics simulations of diffusion in multi-scale structures. This progress is achieved by developing an analytical approximation methodology for solving the model equations. The reported results are applied to analysis and simulations of subcellular processes and to the quantification of their biological functions. © 2013 IOP Publishing Ltd.


Tauber A.I.,Tel Aviv University
Journal of Theoretical Biology | Year: 2015

Three interconnected positions are advocated: (1) although serving as a useful model, the immune self does not exist as such; (2) instead of a self/nonself demarcation, the immune system 'sees' itself, i.e., it does not ignore the 'self' or attack the 'other;' but exhibits a spectrum of responses, which when viewed from outside the system appear as discrimination of 'self' and 'nonself' based on certain criteria of reactivity. When immune reactions are conceived in terms of normal physiology and open exchange with the environment, where borders dividing host and foreign are elusive and changing, host defense is only part of the immune system's functions, which actually comprise two basic tasks: protection, i.e., to preserve host integrity, and maintenance of organismic identity. And thus (3) if the spectrum of immunity is enlarged, differentiating low reactive 'autoimmune' reactions from activated immune responses against the 'other' is only a matter of degree. Simply, all immunity is 'autoimmunity,' and the pathologic state of immunity directed at normal constituents of the organism is a particular case of dis-regulation, which appropriately is designated, autoimmune. Other uses of 'autoimmunity' and its congeners function as the semantic remnants of Burnet's original self/nonself theory and should be replaced. A new nomenclature is proposed, concinnity, which more accurately designates the physiology of the animal's ordinary housekeeping economy mediated by the immune system than 'autoimmunity' when used to describe such normal functions. © 2015 Elsevier Ltd.


Shokef Y.,Tel Aviv University | Shokef Y.,Weizmann Institute of Science | Safran S.A.,Weizmann Institute of Science
Physical Review Letters | Year: 2012

We show how strain stiffening affects the elastic response to internal forces, caused either by material defects and inhomogeneities or by active forces that molecular motors generate in living cells. For a spherical force dipole in a material with a strongly nonlinear strain energy density, strains change sign with distance, indicating that, even around a contractile inclusion or molecular motor, there is radial compression; it is only at a long distance that one recovers the linear response in which the medium is radially stretched. Scaling laws with irrational exponents relate the far-field renormalized strain to the near-field strain applied by the inclusion or active force. © 2012 American Physical Society.


Apter A.,Tel Aviv University
European Psychiatry | Year: 2010

A major hindrance to determining the underlying biology of suicide is the heterogeneity of the phenotype. Not only are there various forms of self-harm and suicidal behaviors but even the finite act of dying by suicide can occur in multiple psychosocial contexts. Of all the different forms of fatal and non-fatal suicidal behaviors, the one that received the most attention is the aggressive impulsive type, which seems to occur in younger people and to cut across nosological entities, although its most classical expression occurs in borderline personality disorder. This focus should not obscure the fact that other forms of suicidal behavior such as those related to demoralization or wounded honor (narcissism) may well have different underlying genetic diatheses. © 2010 Elsevier Masson SAS.


In Alzheimer's disease, soluble amyloid-β causes synaptic dysfunction and neuronal loss. Receptors involved in clearance of soluble amyloid-β are not known. Here we use short hairpin RNA screening and identify the scavenger receptor Scara1 as a receptor for soluble amyloid-β expressed on myeloid cells. To determine the role of Scara1 in clearance of soluble amyloid-β in vivo, we cross Scara1 null mice with PS1-APP mice, a mouse model of Alzheimer's disease, and generate PS1-APP-Scara1-deficient mice. Scara1 deficiency markedly accelerates Aβ accumulation, leading to increased mortality. In contrast, pharmacological upregulation of Scara1 expression on mononuclear phagocytes increases Aβ clearance. This approach is a potential treatment strategy for Alzheimer's disease.


The physical phenomena of plasma plume generation and plasma expansion by target-laser interaction are considered for moderate laser power density. The kinetics of target vaporization, atom ionization, and plasma heating are described. The mechanism of electric sheath formation near the surface, electron emission from the target, and the electrical breakdown phenomena by laser irradiation are analyzed. The plasma expansion is described taking into account the near target plasma structure and the absorption of the laser radiation. The mechanisms accelerating the plasma and generating an electric field in it are discussed. The work reviews experiments and theoretical models and summarizes the results in order to understand the measurements and to discuss open questions. As example, the plasma parameters (electron temperature and density, degree of ionization, and plasma velocity) are calculated for an Ag target using the developed model that considers self-consistently the target heating, kinetics of target evaporation, plasma heating, and ion flux to the target. The calculated ion velocity in the expanding plasma jet is in accordance with the measurement. The ion energy linearly depends on the ion charge state, as observed experimentally. Copyright © 2012 Cambridge University Press.


Benveniste Y.,Tel Aviv University
Journal of the Mechanics and Physics of Solids | Year: 2012

Interphases appear in heterogeneous media in a variety of forms. Often the treatment of a thin interphase as a separate phase in a multiphase solid is not convenient in analytical or numerical solutions of those systems. Thus, approximate models of a thin interphase that make possible to obtain a solution for the fields in the media adjacent to it, without the need of determining the fields within the interphase itself, become a necessity in many cases. The question then arises whether a global property which was present in the original heterogeneous medium will continue to prevail after an approximate representation of the thin interphase has been introduced in the system. A global property, known to have important consequences on the behavior of the heterogeneous solid, is the reciprocity relation between a pair of two different solutions, as stated by the reciprocal theorem. Since the formulation of an approximate model for the thin interphase involves several assumptions, the fulfillment of the reciprocal theorem in the original system does not necessarily imply its fulfillment in the transformed system in which an approximate model of the thin interphase has been intoduced. The preservation of the reciprocity relation by the approximate model, if proved, would be considered to be an important consistency quality of the model. In this paper we consider steady thermal conduction phenomena, and generalize the two approximate models of a thin interphase by Bövik (1994), Benveniste (2006), Benveniste and Berdichevsky (2010) to the case of thin interphases with a variable conductivity. The fulfillment of the reciprocity property in the presence of those models, which was not discussed in the above papers, is investigated here in the context of their presently developed generalized version, and it is proved that both models fulfill the reciprocal theorem. © 2012 Elsevier Ltd.


Netzer H.,Tel Aviv University | Trakhtenbrot B.,Weizmann Institute of Science | Trakhtenbrot B.,ETH Zurich
Monthly Notices of the Royal Astronomical Society | Year: 2014

We investigate the accretion rate, bolometric luminosity, black hole (BH) growth time and BH spin in a large active galactic nucleus (AGN) sample under the assumption that all such objects are powered via thin or slim accretion discs (ADs). We use direct estimates of the mass accretion rate, Ṁ, to show that many currently used values of Lbol and L/LEdd are either underestimated or overestimated because they are based on bolometric correction factors that are adjusted to the properties of moderately accreting AGNs and do not take into account the correct combination of BH mass, spin and accretion rate. The consistent application of AD physics to our sample of Sloan Digital Sky Survey (SDSS) AGNs leads to the following findings. (1) Even the most conservative assumption about the radiative efficiency of fastaccreting BHs shows that many of these sources must contain slim ADs. We illustrate this by estimating the fraction of such objects at various redshifts. (2) Many previously estimated BH growth times are inconsistent with the AD theory. In particular, the growth times of the fastest accreting BHs were overestimated in the past by large factors with important consequences to AGN evolution. (3) Currently used bolometric correction factors for low accretion rate very massive SDSS BHs are inconsistent with the AD theory. Applying the AD set of assumptions to such objects, combined with standard photoionization calculations of broad emission lines, leads to the conclusion that many such objects must contain fast-spinning BHs. © 2013 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.


Frankfurt L.,Tel Aviv University | Guzey V.,Jefferson Lab | Strikman M.,Pennsylvania State University
Physics Reports | Year: 2012

We present and discuss the theory and phenomenology of the leading twist theory of nuclear shadowing which is based on the combination of the generalization of the Gribov-Glauber theory, QCD factorization theorems, and the HERA QCD analysis of diffraction in lepton-proton deep inelastic scattering (DIS). We apply this technique for the analysis of a wide range of hard processes with nuclei-inclusive DIS on deuterons, medium-range and heavy nuclei, coherent and incoherent diffractive DIS with nuclei, and hard diffraction in proton-nucleus scattering-and make predictions for the effect of nuclear shadowing in the corresponding sea quark and gluon parton distributions. We also analyze the role of the leading twist nuclear shadowing in generalized parton distributions in nuclei and in certain characteristics of final states in nuclear DIS. We discuss the limits of applicability of the leading twist approximation for small x scattering off nuclei and the onset of the black disk regime and methods of detecting it. It will be possible to check many of our predictions in the near future in the studies of the ultraperipheral collisions at the Large Hadron Collider (LHC). Further checks will be possible in pA collisions at the LHC and forward hadron production at the Relativistic Heavy Ion Collider (RHIC). Detailed tests will be possible at an Electron-Ion Collider (EIC) in the USA and at the Large Hadron-Electron Collider (LHeC) at CERN. © 2012 Elsevier B.V.


Neistein E.,Max Planck Institute for Extraterrestrial Physics | Netzer H.,Tel Aviv University
Monthly Notices of the Royal Astronomical Society | Year: 2014

We present a new semi-analytic model for the common growth of black holes (BHs) and galaxies within a hierarchical Universe. The model is tuned to match the mass function of BHs at z = 0 and the luminosity functions of active galactic nuclei (AGNs) at z < 4. We use a new observational constraint, which relates the luminosity of AGNs to the star formation rate of their host galaxies. We show that this new constraint is important in various aspects: (a) it indicates that BH accretion events are episodic; (b) it favours a scenario in which BH accretion is triggered by merger events of all mass ratios; (c) it constrains the duration of both merger-induced starbursts and BH accretion events. The model reproduces the observations once we assume that only 4 per cent of the merger events trigger BH accretion; BHs accretion is not related to secular evolution; and only a few per cent of the mass made in bursts goes into the BH. We find that AGNs with low or intermediate luminosity are mostly being triggered by minor merger events, in broad agreement with observations. Our model matches various observed properties of galaxies, such as the stellar mass function at z < 4 and the clustering of galaxies at redshift zero. This allows us to use galaxies as a reliable backbone for BH growth, with reasonable estimates for the frequency of merger events. Other modes of BH accretion, such as disc-instability events, were not considered here, and should be further examined in the future. © 2013 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.


The NAP motif of activity-dependent neuroprotective protein (ADNP) enhanced memory scores in patients suffering from mild cognitive impairment and protected activities of daily living in schizophrenia patients, while fortifying microtubule (MT)-dependent axonal transport, in mice and flies. The question is how does NAP fortify MTs? Our sequence analysis identified the MT end-binding protein (EB1)-interacting motif SxIP (SIP, Ser-Ile-Pro) in ADNP/NAP and showed specific SxIP binding sites in all members of the EB protein family (EB1-3). Others found that EB1 enhancement of neurite outgrowth is attenuated by EB2, while EB3 interacts with postsynaptic density protein 95 (PSD-95) to modulate dendritic plasticity. Here, NAP increased PSD-95 expression in dendritic spines, which was inhibited by EB3 silencing. EB1 or EB3, but not EB2 silencing inhibited NAP-mediated cell protection, which reflected NAP binding specificity. NAPVSKIPQ (SxIP=SKIP), but not NAPVAAAAQ mimicked NAP activity. ADNP, essential for neuronal differentiation and brain formation in mouse, a member of the SWI/SNF chromatin remodeling complex and a major protein mutated in autism and deregulated in schizophrenia in men, showed similar EB interactions, which were enhanced by NAP treatment. The newly identified shared MT target of NAP/ADNP is directly implicated in synaptic plasticity, explaining the breadth and efficiency of neuroprotective/neurotrophic capacities.Molecular Psychiatry advance online publication, 2 September 2014; doi:10.1038/mp.2014.97.


Shmueli U.,Tel Aviv University
Journal of Applied Crystallography | Year: 2012

This article briefly summarizes the ideal structure-factor statistics, which are usually the only ones that are applied at the stage of resolution of space-group ambiguities, and points out their disadvantages. Next, the non-ideal structure-factor statistics, i.e. those taking any atomic composition into account, are summarized and applied to several examples, based on real intensity data. The superiority of the non-ideal statistics, when applied to the problematic space group , is obvious. It is also shown that statistics for some orthorhombic space groups are rather insensitive to atomic heterogeneity. A table of coefficients is presented from which non-ideal statistics can be computed for all the space groups of the triclinic, monoclinic and orthorhombic systems. © 2012 International Union of Crystallography Printed in Singapore-all rights reserved.


Lahav O.,Tel Aviv University
Proceedings - Symposium on Logic in Computer Science | Year: 2013

We provide a general method for generating cut-free and/or analytic hyper sequent Gent Zen-type calculi for a variety of normal modal logics. The method applies to all modal logics characterized by Kripke frames, transitive Kripke frames, or symmetric Kripke frames satisfying some properties, given by first-order formulas of a certain simple form. This includes the logics KT, KD, S4, S5, K4D, K4.2, K4.3, KBD, KBT, and other modal logics, for some of which no Gentzen calculi was presented before. Cut-Admissibility (or analyticity in the case of symmetric Kripke frames) is proved semantically in a uniform way for all constructed calculi. The decidability of each modal logic in this class immediately follows. © 2013 IEEE.


A recently proposed method for the calculation of the effective electronic coupling (or charge-transfer integral) in a two-state system is discussed and related to other methods in the literature. The theoretical expression of the coupling is exact within the two-state model and applies to the general case where the charge transfer (CT) process involves nonorthogonal initial and final diabatic (localized) states. In this work, it is shown how this effective electronic coupling is also the one to be used in a suitable extension of Rabis formula to the nonorthogonal representation of two-state dynamical problems. The formula for the transfer integral is inspected in the regime of long-range CT and applied to CT reactions in redox molecular systems of interest to biochemistry and/or to molecular electronics: the guanine-thymine stack from regular B-DNA, the polyaromatic perylenediimide stack, and the quinol-semiquinone couple. The calculations are performed within the framework of the Density Functional Theory (DFT), using hybrid exchange-correlation (XC) density functionals, which also allowed investigation of the appropriateness of such hybrid-DFT methods for computing electronic couplings. The use of the recently developed M06-2X and M06-HF density functionals in appropriate ways is supported by the results of this work. © 2011 American Chemical Society.


Nelson N.,Tel Aviv University | Junge W.,University of Osnabruck
Annual Review of Biochemistry | Year: 2015

Oxygenic photosynthesis is the principal converter of sunlight into chemical energy on Earth. Cyanobacteria and plants provide the oxygen, food, fuel, fibers, and platform chemicals for life on Earth. The conversion of solar energy into chemical energy is catalyzed by two multisubunit membrane protein complexes, photosystem I (PSI) and photosystem II (PSII). Light is absorbed by the pigment cofactors, and excitation energy is transferred among the antennae pigments and converted into chemical energy at very high efficiency. Oxygenic photosynthesis has existed for more than three billion years, during which its molecular machinery was perfected to minimize wasteful reactions. Light excitation transfer and singlet trapping won over fluorescence, radiation-less decay, and triplet formation. Photosynthetic reaction centers operate in organisms ranging from bacteria to higher plants. They are all evolutionarily linked. The crystal structure determination of photosynthetic protein complexes sheds light on the various partial reactions and explains how they are protected against wasteful pathways and why their function is robust. This review discusses the efficiency of photosynthetic solar energy conversion. Copyright © 2015 by Annual Reviews. All rights reserved.


Junge W.,University of Osnabruck | Nelson N.,Tel Aviv University
Annual Review of Biochemistry | Year: 2015

Oxygenic photosynthesis is the principal converter of sunlight into chemical energy. Cyanobacteria and plants provide aerobic life with oxygen, food, fuel, fibers, and platform chemicals. Four multisubunit membrane proteins are involved: photosystem I (PSI), photosystem II (PSII), cytochrome b6f (cyt b6f), and ATP synthase (FOF1). ATP synthase is likewise a key enzyme of cell respiration. Over three billion years, the basic machinery of oxygenic photosynthesis and respiration has been perfected to minimize wasteful reactions. The proton-driven ATP synthase is embedded in a proton tight-coupling membrane. It is composed of two rotary motors/generators, FO and F1, which do not slip against each other. The proton-driven FO and the ATP-synthesizing F1 are coupled via elastic torque transmission. Elastic transmission decouples the two motors in kinetic detail but keeps them perfectly coupled in thermodynamic equilibrium and (time-averaged) under steady turnover. Elastic transmission enables operation with different gear ratios in different organisms. Copyright © 2015 by Annual Reviews. All rights reserved.


Noninvasive prenatal testing using cell-free DNA in maternal blood for trisomy 21 was introduced in 2011. This technology has continuously evolved with the addition of screening for trisomy 18 and trisomy 13 followed by the inclusion of sex chromosome aneuploidies. Expanded noninvasive prenatal test panels have recently become available, which enable screening for microdeletion syndromes such as the 22q11.2 deletion (associated with the velocardiofacial syndrome) and others. However, the performance data for these microdeletion syndromes are derived from a small number of samples, mostly generated in vitro. Rigorous performance evaluation, as was done at least for trisomy 21 testing using cell-free DNA analysis, is difficult to perform given the rarity of each condition. In addition, detection rates may vary considerably depending on deletion size. Importantly, positive predictive values (PPVs), strongly influenced by the low prevalence, are expected to be significantly lower than 10% for most conditions. Thus, screening in an average-risk population is likely to have many more false-positives than affected cases detected. Conversely, testing in a high-risk population such as fetuses with cardiac anomalies may have higher PPVs, but a negative result needs to be considered carefully as a result of uncertain information about detection rates and a significant residual risk for other copy number variants and single gene disorders. This article integrates current knowledge on cell-free DNA testing for microdeletions with the aim to assist clinicians and policymakers in designing optimal programs for screening in pregnancy. © 2015 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.


Netzer H.,Tel Aviv University
Annual Review of Astronomy and Astrophysics | Year: 2015

This review describes recent developments related to the unified model of active galactic nuclei (AGNs). It focuses on new ideas about the origin and properties of the central obscurer (torus) and the connection to its surroundings. The review does not address radio unification. AGN tori must be clumpy but uncertainties about their properties persist. Today's most promising models involve disk winds of various types and hydrodynamic simulations that link the large-scale galactic disk to the inner accretion flow. Infrared (IR) studies greatly improved our understanding of the spectral energy distribution of AGNs, but they are hindered by various selection effects. X-ray samples are more complete. The dependence of the covering factor of the torus on luminosity is a basic relationship that remains unexplained. There is also much confusion regarding real type-II AGNs, which do not fit into a simple unification scheme. The most impressive recent results are due to IR interferometry, which is not in accord with most torus models, and the accurate mapping of central ionization cones. AGN unification may not apply to merging systems and is possibly restricted to secularly evolving galaxies. © 2015 by Annual Reviews.


Rozen S.,Tel Aviv University
Accounts of Chemical Research | Year: 2014

ConspectusThe complex HOF·CH3CN is readily obtained by bubbling dilute fluorine into aqueous acetonitrile solution. It does not have to be purified or isolated, and its solution can react as is, after the concentration has been establish by any iodometric method. It is the only reagent possessing a distinctive positive oxygen species. This enables electrophilic oxygen transfer with results no other reagent can match. HOF·CH3CN demonstrates its ability in epoxidations that either could not be performed before or could only obtained 5 orders of magnitude slower. This complex is also an excellent tool for oxygenation of compounds at the α position of a carbonyl, including the synthesis of some hard-to-come-by indanediones, which are important for fingerprint visualization on paper. HOF·CH3CN proves itself as a very efficient reagent for oxygenating tertiary nitrogen atoms both in aliphatic (including azides) and in aromatic amines, which could not be accomplished despite many attempts in the last 50 years. Oxygenation of two tertiary nitrogen atoms in the same molecule also becomes feasible as demonstrated for various phenanthrolines, bipyridines, diazafluorenones, and quinoxalines. It was also used to oxygenate primary amines, and because of the exceptionally mild conditions, it could transform vicinal aliphatic diamines to vicinal dinitro derivatives as well as amino acids to the corresponding nitro ones, practically unknown transformations before. Its ability to react with azines and hydrazones and convert them to the original carbonyls helped to establish these groups as good protecting tools for a variety of carbonyls.HOF·CH3CN excels in oxygenation of various sulfur and selenium compounds that could not be oxygenated in the past. The selectivity of the oxidation is quite good, and if there are alcohols, double bonds, and sulfides in the same molecule, usually the sulfur atom will be attacked first. Of special interest is the reaction with oligothiophenes resulting at will in either [all]-S,S-dioxooligothiophenes or in partially oxygenated ones. Some of these last derivatives have the narrowest HOMO-LUMO gap of all oligothiophenes tested, a very desirable feature. This reagent can also oxidize thiols or disulfides to either sulfonic or sulfinic acids at will, all in seconds and in very high yields.Since the oxygen atom of HOF·CH 3CN originates in water, it is very easy and relatively inexpensive to introduce the heavy oxygen isotope in many sites of a variety of molecules, some of them quite important. The 18O tirapazamine and any desirable alcohol, R(Ar)18OH, are two examples. © 2014 American Chemical Society.


Ben-Jacob E.,Tel Aviv University | Ben-Jacob E.,Rice University | Coffey D.,Johns Hopkins University | Levine H.,Rice University
Trends in Microbiology | Year: 2012

Despite decades of a much improved understanding of cancer biology, we are still baffled by questions regarding the deadliest traits of malignancy: metastatic colonization, dormancy and relapse, and the rapid evolution of multiple drug and immune resistance. New ideas are needed to resolve these critical issues. Relying on finding and demonstrating parallels between collective behavior capabilities of cancer cells and that of bacteria, we suggest communal behaviors of bacteria as a valuable model system for new perspectives and research directions. Understanding the ways in which bacteria thrive in competitive habitats and their cooperative strategies for surviving extreme stress can shed light on cooperativity in tumorigenesis and portray tumors as societies of smart communicating cells. This may translate into progress in fathoming cancer pathogenesis. We outline new experiments to test the cancer cooperativity hypothesis and reason that cancer may be outsmarted through its own 'social intelligence'. © 2012 Elsevier Ltd.


Ormianer Z.,Tel Aviv University
The International journal of oral & maxillofacial implants | Year: 2012

This study is a retrospective assessment of the long-term efficacy of dental implant therapy in periodontally susceptible patients. A private-practice chart review was conducted to identify partially dentate subjects treated with implant-supported restorations that had been monitored annually for at least 9.5 years. Subjects were assigned to either a periodontal group or a control group according to their health histories. Data were entered into spreadsheets on a personal computer and analyzed statistically with dedicated software. Thirty periodontal subjects were treated with 138 implants and 45 prostheses, and 16 control subjects were treated with 35 implants and 21 prostheses. The mean follow-up was 130 months. One implant failed before loading in the periodontal group. Cumulative 10-year survival rates were 99.3% (n = 137/138) for periodontal implants and 100% (n = 35/35) for control implants. Most surviving implants had no bone loss (n = 109/172, 63.4%). Most of the surviving implants with bone loss (n = 63/172, 36.6%) were concentrated in the periodontal cohort (90%, n = 57/63) and among women (60%, n = 15/25) regardless of cohort. Prosthesis failure was 25.2% (n = 16/66), with 12 porcelain fractures, 2 cement failures, and 2 framework fractures. In all cases, failed prostheses were immediately replaced and patients continued to function. Periodontal susceptibility resulted in increased bone loss but did not affect implant survival. The cause of greater bone loss in women could not be determined from the data but may have been related to the postmenopausal status of the subject population (mean age = 54 years).


The insulin-like growth factor (IGF) axis mediates growth, differentiation and developmental processes, and is also involved in control of metabolic activities. Deregulation of IGF axis expression and action is linked to a number of pathologies, ranging from metabolic disorders to growth deficits and cancer development. Activation of the IGF signaling pathway is a crucial prerequisite for malignant transformation. In addition, overexpression of the IGF-1 receptor (IGF-1R) constitutes a typical hallmark of most types of cancer. A series of tumor suppressors have been identified whose mechanisms of action involve transcriptional suppression of the IGF-1R gene. These tumor suppressors include the p53/p63/p73 family, breast cancer gene-1, von-Hippel Lindau protein, Wilms tumor-1 and others. Comprehensive analyses have identified a complex bidirectional interplay between the IGF and tumor-suppressor signaling pathways. These interactions are of major importance in terms of cancer development and may also predict responsiveness to IGF-1R-targeted therapies. Furthermore, the insulin/IGF system has a pivotal role in the regulation of cancer cell metabolism. Deregulation of IGF axis components by mutated tumor-suppressor proteins may lead to metabolic perturbations, with ensuing pathological consequences. © 2012 Macmillan Publishers Limited All rights reserved.


Benveniste Y.,Tel Aviv University | Milton G.W.,University of Utah
Journal of the Mechanics and Physics of Solids | Year: 2010

The effective medium approximation (EMA) and the average field approximation (AFA) are two classical micromechanics models for the determination of effective properties of heterogeneous media. They are also known in the literature as 'self-consistent' approximations. In the AFA, the basic idea is to estimate the actual average field existing in a phase through a configuration in which a typical particle of that phase is embedded in the homogenized medium. In the EMA, on the other hand, one or more representative microstructural elements of the composite is embedded in the homogenized effective medium subjected to a uniform field, and the demand is made that the dominant part of the far-field disturbance vanishes. Both parts of this study are concerned with two-phase, matrix-based, effectively isotropic composites with an inclusion phase consisting of randomly oriented particles of arbitrary shape in general, and ellipsoidal shape in particular. The constituent phases are assumed to be isotropic. It is shown that in those systems the AFA and EMA give different predictions, with the distinction between them becoming especially striking regarding their standing vis-vis the HashinShtrikman (HS-bounds). While due to its realizability property the EMA will always obey the bounds, we show that there are circumstances in which the AFA may violate the bounds. In the AFA for two-phase matrix-based composites, the embedded inclusion is a particle of the inclusion phase. If the particle is directly embedded in the effective medium, the method is called here the self-consistent schemeaverage field approximation (SCS-AFA), and will obey the HS-bounds for an inclusion shape that is simply connected. If the embedded entity is a matrix-coated particle, then the method is called the generalized self-consistent schemeaverage field approximation (GSCS-AFA), and may violate the HS-bounds. On the other hand, in the EMA for matrix-based composites with well-separated inclusions, we indicate that in view of its premises the embedding with a matrix-coated particle generally becomes the appropriate one, and the method is thus called the generalized self-consistent schemeeffective medium approximation (GSCS-EMA). Part I of this study is concerned with SCS-AFA in dielectrics and elasticity, and Part II with the GSCS-AFA and GSCS-EMA in dielectrics. © 2010 Elsevier Ltd.


Dubi Y.,University of California at San Diego | Dubi Y.,Tel Aviv University | Di Ventra M.,University of California at San Diego
Reviews of Modern Physics | Year: 2011

Advances in the fabrication and characterization of nanoscale systems now allow for a better understanding of one of the most basic issues in science and technology: the flow of heat at the microscopic level. In this Colloquium recent advances are surveyed and an understanding of physical mechanisms of energy transport in nanostructures is presented, focusing mainly on molecular junctions and atomic wires. Basic issues are examined such as thermal conductivity, thermoelectricity, local temperature and heating, and the relation between heat current density and temperature gradient-known as Fourier's law. Both theoretical and experimental progress are critically reported in each of these issues and future research opportunities in the field are discussed. © 2011 American Physical Society.


A general integral method is presented for calculating the dipolophoretic velocities of two interacting, ideally polarizable colloids of arbitrary electric double layer thickness under weak AC electric forcing. The 12 non-linear mobilities are comprised of induced-charge-electrophoresis (ICEP), dielectrophoresis (DEP), and Faxén-Stokes contributions. The explicit integral scheme, based on the Teubner [J. Chem. Phys. 76, 5564 (1982)] formulation, is demonstrated for the case of two-sphere interaction. Further simplifications using the remote-sphere approximation are employed and the asymptotic results thus obtained are compared against those recently obtained by Saintillan [Phys. Fluids 20, 067104 (2008)] and extend the latter for finite Debye scales and forcing frequencies. It is also shown that the same methodology can be used to determine the mobility of a polarized particle in the proximity of an insulating or conducting plane boundary. The case of a spherical colloid near an uncharged insulating planar wall is of special interest and by using the Lorentz image solution, we readily recover the large-spacing approximation of Yariv [Proc. R. Soc. A. London Ser. A 465, 709 (2009)] as a limiting case. © 2011 American Institute of Physics.


Eliazar I.,Holon Institute of Technology | Klafter J.,Tel Aviv University
Annals of Physics | Year: 2011

Brownian motion is widely considered the quintessential model of diffusion processes-the most elemental random transport processes in Science and Engineering. Yet so, examples of diffusion processes displaying highly non-Brownian statistics-commonly termed "Anomalous Diffusion" processes-are omnipresent both in the natural sciences and in engineered systems. The scientific interest in Anomalous Diffusion and its applications is growing exponentially in the recent years. In this Paper we review the key statistics of Anomalous Diffusion processes: sub-diffusion and super-diffusion, long-range dependence and the Joseph effect, Lévy statistics and the Noah effect, and 1/f noise. We further present a theoretical model-generalizing the Einstein-Smoluchowski diffusion model-which provides a unified explanation for the prevalence of Anomalous Diffusion statistics. Our model shows that what is commonly perceived as "anomalous" is in effect ubiquitous. © 2011 Elsevier Inc.


Korczyn A.D.,Tel Aviv University
Nature Reviews Neurology | Year: 2015

Parkinson disease is a primary degenerative disease of the brain, but parkinsonism can also result from a variety of vascular disorders. Vascular parkinsonism (VP) most frequently presents as lower body parkinsonism, a condition that is accompanied by the development of white matter lesions (WMLs) and lacunes in the brain. Patients with lower body parkinsonism exhibit gait impairment and go on to develop urinary incontinence, abnormal pyramidal responses and cognitive decline. However, WMLs and lacunes are also common observations among elderly individuals who do not have parkinsonism, which causes difficulty in determining the pathogenetic mechanisms that lead to VP. In addition, imaging studies suggest that many pathological and clinical features are common to VP and Binswanger disease, a type of small vessel vascular dementia. This Review summarizes current understanding of the clinical characteristics of VP, as well as knowledge gained from neuroimaging and nuclear imaging of the pathological features of VP. The lack of current treatment options, and the emergence of new therapies such as cerebrospinal fluid drainage, are also discussed. Finally, consideration is given to whether the overlap between VP and Binswanger disease means that these two disorders should be considered as part of the same disease entity. © 2015 Macmillan Publishers Limited.


Gruss E.,Tel Aviv University
Classical and Quantum Gravity | Year: 2011

We consider Hoava gravity coupled to Maxwell and higher derivative magnetic terms. We construct static spherically symmetric black hole solutions in the low-energy approximation. We calculate the horizon locations and temperatures in the near-extremal limit, for asymptotically flat and (anti-)de Sitter spaces. We also construct a detailed balanced version of the theory, for which we find projectable and non-projectable, non-perturbative solutions. © 2011 IOP Publishing Ltd.


Regev O.,Tel Aviv University
Proceedings of the Annual IEEE Conference on Computational Complexity | Year: 2010

In this survey we describe the Learning with Errors (LWE) problem, discuss its properties, its hardness, and its cryptographic applications. © 2010 IEEE.


Donnelly J.P.,Radboud University Nijmegen | Lahav M.,Tel Aviv University
Journal of Antimicrobial Chemotherapy | Year: 2012

Mucormycosis can be devastating and, as yet, there are no ideal therapies available. Observations that iron chelation may be a useful adjunct to antifungal treatment encouraged Spellberg et al. (J Antimicrob Chemother 2012; 715-22) to undertake a trial of deferasirox combined with liposomal amphotericin B (AmBisome®) as short-term therapy for mucormycosis. The results were disappointing as patients treated with deferasirox had a higher mortality rate at 90 days, leading the authors to conclude that the data did not support a role for initial, adjunctive deferasirox therapy for mucormycosis. We review the issues arising from this study to help decide whether the evidence that now exists supports further studies or represents the end of this line of enquiry. © The Author 2011. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.


Yeredor A.,Tel Aviv University
IEEE Transactions on Signal Processing | Year: 2010

We consider the separation of Gaussian sources exhibiting general, arbitrary (not necessarily stationary) covariance structures. First, assuming a semi-blind scenario, in which the sources' covariance structures are known, we derive the maximum likelihood estimate of the separation matrix, as well as the induced CramrRao lower bound (iCRLB) on the attainable Interference to Source Ratio (ISR). We then extend our results to the fully blind scenario, in which the covariance structures are unknown. We show that (under a scaling convention) the Fisher information matrix in this case is block-diagonal, implying that the same iCRLB (as in the semi-blind scenario) applies in this case as well. Subsequently, we demonstrate that the same semi-blind optimal performance can be approached asymptotically in the fully blind scenario if the sources are sufficiently ergodic, or if multiple snapshots are available. © 2010 IEEE.


Hanein Y.,Tel Aviv University
Physica Status Solidi (B) Basic Research | Year: 2010

After two decades of extensive investigation into the unique properties of carbon nanotubes (CNTs), the focus is now shifting toward the utilization of CNTs in real applications. Of particular interest is the use of CNTs in microtechnologies. To this end, CNT integration methods have to be optimized to guarantee yield, low-cost, and high performances. Here we describe three general schemes which we developed over the past several years which facilitate the direct integration of CNTs into microfabricated devices in a seamless manner. Using the chemical vapor deposition (CVD) method, and carefully designed pre-patterned substrates, tubes can be easily deposited at very high fidelity. Through these integration schemes, the CNT growth step becomes equivalent to many other deposition steps of other materials. Using the processes we developed, a substrate can be introduced into the CNT CVD system and CNTs will grow at the right location to match the specific application. We briefly demonstrate two applications for which these techniques may be applied.TEM image of a CNT grown on a grid showing the strong surface effects on CNT growth. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Osherov N.,Tel Aviv University
Frontiers in Microbiology | Year: 2012

Aspergillus fumigatus is an opportunistic environmental mold that can cause severe allergic responses in atopic individuals and poses a life-threatening risk for severely immunocompromised patients. Infection is caused by inhalation of fungal spores (conidia) into the lungs. The initial point of contact between the fungus and the host is a monolayer of lung epithelial cells. Understanding how these cells react to fungal contact is crucial to elucidating the pathobiology of Aspergillus-related disease states. The experimental systems, both in vitro and in vivo, used to study these interactions, are described. Distinction is made between bronchial and alveolar epithelial cells. The experimental findings suggest that lung epithelial cells are more than just "innocent bystanders" or a purely physical barrier against infection. They can be better described as an active extension of our innate immune system, operating as a surveillance mechanism that can specifically identify fungal spores and activate an offensive response to block infection. This response includes the internalization of adherent conidia and the release of cytokines, antimicrobial peptides, and reactive oxygen species. In the case of allergy, lung epithelial cells can dampen an over-reactive immune response by releasing anti-inflammatory compounds such as kinurenine. This review summarizes our current knowledge regarding the interaction of A. fumigatus with lung epithelial cells. A better understanding of the interactions between A. fumigatus and lung epithelial cells has therapeutic implications, as stimulation or inhibition of the epithelial response may alter disease outcome. © 2012 Osherov.


Hollander N.,Tel Aviv University
Frontiers in Immunology | Year: 2012

Therapy for non-Hodgkin's lymphoma has progressed significantly over the last decades. However, the majority of patients remain incurable, and novel therapies are needed. Because immunotherapy ideally offers target selectivity, an ever increasing number of immunotherapies, both passive and active, are undergoing development. The champion of passive immunotherapy to date is the anti-CD20 monoclonal antibody rituximab that revolutionized the standard of care for lymphoma. The great success of rituximab catalyzed the development of new passive immunotherapy strategies that are currently undergoing clinical evaluation. These include improvement of rituximab efficacy, newer generation anti-CD20 antibodies, drug-conjugated and radio labeled anti-CD20 antibodies, monoclonal antibodies targeting non-CD20 lymphoma antigens, and bispecific antibodies. Active immunotherapy aims at inducing long-lasting antitumor immunity, thereby limiting the likelihood of relapse. Current clinical studies of active immunotherapy for lymphoma consist largely of vaccination and immune checkpoint blockade. A variety of proteinand cell-based vaccines are being tested in ongoing clinical studies. Recently completed phase III clinical trials of an idiotype protein vaccine suggest that the vaccine may have clinical activity in a subset of patients. Efforts to enhance the efficacy of active immunotherapy are ongoing with an emphasis on optimization of antigen delivery and presentation of vaccines and modulation of the immune system toward counteracting immunosuppression, using antibodies against immune regulatory checkpoints. This article discusses results of the various immunotherapy approaches applied to date for B-cell lymphoma and the ongoing trials to improve their effect. © 2012 Hollander.


He Y.,Guangdong Polytechnic Normal University | Malomed B.A.,Tel Aviv University
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2013

We demonstrate the existence of two species of stable bright solitons, fundamental and dipole, in one-dimensional self-defocusing nonlocal media, with the local value of nonlinearity coefficient having one or several minima and growing at any rate faster than |x| at large values of coordinate x. The model can be derived for a slab optical waveguide with thermal nonlinearity. The most essential difference from the local counterpart of this system is the competition between two different spatial scales, one determining the modulation pattern of the nonlinearity coefficient and the other being the correlation length of the nonlocality. The competition is explicitly exhibited by an analytically obtained asymptotic form of generic solutions. Particular exact solutions are found analytically, and full soliton families are constructed in a numerical form. The multichannel settings, with two or three local minima of the nonlinearity coefficient, are considered here for both local and nonlocal models of the present type. States with multiple solitons launched into different channels are stable if the spacing between them exceeds a certain minimum value. A regime of stable Josephson oscillations of solitons between parallel channels is reported too. © 2013 American Physical Society.


Helled R.,Tel Aviv University
Astrophysical Journal Letters | Year: 2012

We explore the change in Jupiter's normalized axial moment of inertia (NMOI) assuming that Jupiter undergoes core erosion. It is found that Jupiter's contraction combined with an erosion of 20 M ⊕ from a primordial core of 30M ⊕ can significantly change Jupiter's NMOI over time. It is shown that Jupiter's NMOI could have changed from 0.235 to 0.264 throughout its evolution. We find that an NMOI value of 0.235 as suggested by dynamical models could, in principle, be consistent with Jupiter's primordial internal structure. Low NMOI values, however, persist only for the first 106years of Jupiter's evolution. Re-evaluation of dynamical stability models as well as more sophisticated evolution models of Jupiter with core erosion seem to be required in order to provide more robust estimates for Jupiter's primordial NMOI. © 2012. The American Astronomical Society. All rights reserved.


Shoenfeld Y.,Tel Aviv University
BMC medicine | Year: 2013

In this Q&A, we talk to Professor Yehuda Shoenfeld about Autoimmune Syndrome Induced by Adjuvants (ASIA) and discuss his recommendations regarding further research in the field.


We study the field enhancement and resonance frequencies in split-ring resonators (SRR) illuminated by azimuthally polarized light. We find that compared to linearly polarized illumination, the azimuthally polarized illumination increase the intensity enhancement by more than an order of magnitude. We attribute the increase in the intensity enhancement to the improved overlap between the SRR geometry and the direction of the electric field vector at each point. In addition, we present and explore a method to tune the resonance frequency of the SRR (for azimuthal polarization) by introducing more gaps in the structure. This approach allows for simple and straightforward tuning of the resonance frequency with small impact on the intensity enhancement. The impact of the design parameters on the intensity enhancement under azimuthally polarized illumination is also studied in details, exhibiting clear differences compared to the case of linear polarized illumination. © 2011 Optical Society of America.


Brainerd C.J.,Cornell University | Gomes C.F.A.,Cornell University | Moran R.,Tel Aviv University
Psychological Review | Year: 2014

Recollection is currently modeled as a univariate retrieval process in which memory probes provoke conscious awareness of contextual details of earlier target presentations. However, that conception cannot explain why some manipulations that increase recollection in recognition experiments suppress false memory in false memory experiments, whereas others increase false memory. Such contrasting effects can be explained if recollection is bivariate-if memory probes can provoke conscious awareness of target items per se, separately from awareness of contextual details, with false memory being suppressed by the former but increased by the latter. Interestingly, these 2 conceptions of recollection have coexisted for some time in different segments of the memory literature. Independent support for the dualrecollection hypothesis is provided by some surprising effects that it predicts, such as release from recollection rejection, false persistence, negative relations between false alarm rates and target remember/ know judgments, and recollection without remembering. We implemented the hypothesis in 3 bivariate recollection models, which differ in the degree to which recollection is treated as a discrete or a graded process: a pure multinomial model, a pure signal detection model, and a mixed multinomial/signal detection model. The models were applied to a large corpus of conjoint recognition data, with fits being satisfactory when both recollection processes were present and unsatisfactory when either was deleted. Factor analyses of the models' parameter spaces showed that target and context recollection never loaded on a common factor, and the 3 models converged on the same process loci for the effects of important experimental manipulations. Thus, a variety of results were consistent with bivariate recollection. © 2014 American Psychological Association.


Zhao X.,University of Oxford | Weiss G.,Tel Aviv University
IEEE Transactions on Automatic Control | Year: 2011

We consider coupled systems consisting of a well-posed and strictly proper (hence regular) subsystem and a finite-dimensional subsystem connected in feedback. The external world interacts with the coupled system via the finite-dimensional part, which receives the external input and sends out the output. Under several assumptions, we derive well-posedness, regularity, exact (or approximate) controllability and exact (or approximate) observability results for such coupled systems. © 2010 IEEE.


Eliazar I.,Tel Aviv University
Annals of Physics | Year: 2014

Lévy distributions are of prime importance in the physical sciences, and their universal emergence is commonly explained by the Generalized Central Limit Theorem (CLT). However, the Generalized CLT is a geometry-less probabilistic result, whereas physical processes usually take place in an embedding space whose spatial geometry is often of substantial significance. In this paper we introduce a model of random effects in random environments which, on the one hand, retains the underlying probabilistic structure of the Generalized CLT and, on the other hand, adds a general and versatile underlying geometric structure. Based on this model we obtain geometry-based counterparts of the Generalized CLT, thus establishing a geometric theory for Lévy distributions. The theory explains the universal emergence of Lévy distributions in physical settings which are well beyond the realm of the Generalized CLT. © 2014 Elsevier Inc.


Vaidman L.,Tel Aviv University
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2016

Bartkiewicz et al. [2aaPhys. Rev. A 91, 012103 (2015)PLRAAN1050-294710.1103/PhysRevA.91.012103] provided an alternative analysis of an experiment performed by Danan et al. [1abPhys. Rev. Lett. 111, 240402 (2013)PRLTAO0031-900710.1103/PhysRevLett.111.240402] which presented surprising evidence regarding the past of photons passing through an interferometer. They argued that the quantity used by Danan et al. is not a suitable which-path witness, and proposed an alternative. The weaknesses of the analysis are discussed, and it is argued that the alternative, analyzed properly, provides no new predictions. © 2016 American Physical Society.


Vaidman L.,Tel Aviv University
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2016

Potoček and Ferenczi [Phys. Rev. A 92, 023829 (2015)PLRAAN1050-294710.1103/PhysRevA.92.023829] provided an analysis of the experimental evidence obtained by Danan et al. [Phys. Rev. Lett. 111, 240402 (2013)10.1103/PhysRevLett.111.240402] for the surprising behavior of photons passing through an interferometer, in particular, motion on disconnected paths. Potoček and Ferenczi reproduced the results of the experiment, but when analyzing its modification, they claimed that the reasoning of Danan et al., which led to disconnected paths, is erroneous. It is argued here that the criticism of Potoček and Ferenczi is unfounded. © 2016 American Physical Society.


Karliner M.,Tel Aviv University
Acta Physica Polonica B | Year: 2016

I discuss the experimental evidence for and theoretical interpretation of the new mesons and baryons with two heavy quarks. These include doublyheavy baryons, exotic hadronic quarkonia and, most recently, a manifestly exotic pentaquark-like doubly heavy baryon discovered by LHCb with a minimal quark content uudc¯c. Its mass, decay mode and width are in agreement with a prediction based on a physical picture of a deuteron-like ΣcD¯∗ "hadronic molecule". In the second part of the paper, I focus on possible ways of experimental exploration of this new spectroscopy of QCD, especially in future high-energy e+e- colliders with very high luminosity. The primary task of these machines is searching for physics beyond the Standard Model. Consequently, their planned CM energy is far above the relevant energy scale for production of the new doubly-heavy hadrons. Yet, preliminary analysis of radiative-return processes indicates rather high effective luminosity at CM energies of interest, suggesting a possibility for copious production.


Malomed B.A.,Tel Aviv University
Journal of the Optical Society of America B: Optical Physics | Year: 2014

The creation of stable 1D and 2D localized modes in lossy nonlinear mediais a fundamental problem in optics and plasmonics. This article gives a mini review of theoretical methods elaborated on for this purpose, using localized gain applied at one or several hot spots (HS). The introduction surveys a broad class of models for which this approach was developed. Other sections focus in some detail on basic 1D continuous and discrete systems, where the results can be obtained, partly or fully, in an analytical form (and verified by comparison with numerical results), which provides deeper insight into the nonlinear dynamics of optical beams in dissipative nonlinear media. Considered, in particular, are the single and double HS in the usual waveguide with the self-focusing (SF) or self-defocusing (SDF) Kerr nonlinearity, which gives rise to rather sophisticated results in spite of apparent simplicity of the model, solitons attached to a PT-symmetric dipole embedded into the SF or SDF medium, gap solitons pinned to an HS in a Bragg grating, and discrete solitons in a 1D lattice with a hot site. © 2014 Optical Society of America.


Contini M.,Tel Aviv University
Monthly Notices of the Royal Astronomical Society | Year: 2013

The line and continuum spectra of the merger galaxy Arp 220 are analysed with the aim of investigating the ionizing and heating sources. We refer to radio, optical, infrared and X-ray spectra. The results show that in agreement with other merger galaxies, the optical lines are emitted from gas photoionized by the active galactic nucleus (AGN) and heated by the shocks in the extended narrow-line region (ENLR). The infrared lines are better explained by the emission from gas close to the starburst. The starburst dominates the infrared emission. [O I] and [C I] lines in the far-infrared are formed in the internal region of extended clouds and are therefore absorbed, while [C II] lines are emitted from the external edges of outflowing clouds. The O/H relative abundances are about solar and N/H are higher than solar by a factor of ~1.5, throughout the starburst region, while in the AGN ENLR the O/H ratio is half-solar. A relatively high dust-to-gas ratio is indicated by modelling the dust-reprocessed radiation peak consistently with bremsstrahlung emitted from the blackbody radiation-dominated clouds. The observed radio emission is thermal bremsstrahlung, while synchrotron radiation created by the Fermi mechanism at the shock front is absorbed. ©2012 The Author Published by Oxford University Press on behalf of the Royal Astronomical Society.


Gershon E.,Tel Aviv University
IEEE Transactions on Automatic Control | Year: 2013

A method for designing reduced-order output-feedback controllers for linear time-invariant retarded systems with state-multiplicative Wiener-type noise is introduced, which achieves a minimum bound on the H∞ performance level. A cost function is defined that is the expected value of the standard H∞ performance cost with respect to the stochastic parameters. A solution is thus obtained, for the reduced-order H∞ output-feedback control problem, for the stationary case, via the input-output approach where the system is replaced by a non-retarded one, that contains deterministic norm-bounded uncertainties. The results achieved for the nominal case are extended to the uncertain case where the system matrices reside in a given polytope. A numerical example, taken from the field of aircraft control, is given that demonstrates the applicability of the theory developed. © 2013 IEEE.


Neudorfer M.,Tel Aviv University
Investigative ophthalmology & visual science | Year: 2012

We investigated the optical density characteristics of 3subretinal spaces in neovascular age-related macular degeneration (AMD), diabetic retinopathy (DR), rhegmatogenous retinal detachment (RRD), central serous retinopathy (CSR), retinoschisis (RS), and pseudophakic cystoids macular edema (PCME). Patients in whom subretinal fluid (SRF) was detected by optical coherence tomography (OCT), and whose earliest OCT scans showed sufficient SRF for sampling that did not include tissue edges, were chosen for study. The highest quality B-scan containing SRF (as graded by the OCT image acquisition software) was analyzed. Optical density measurements were obtained using ImageJ, an open code Java-based image processing software. The diagnoses of the 71 patients who met the inclusion criteria were AMD in 17, DR in 7, RRD in 18, CSR in 17, RS in 8, and PCME in 4. Optical density ratios (ODRs) were calculated as SRF OD divided by vitreous OD. ODRs were significantly higher in patients with AMD, DR, CSR, and PCME than in those with RRD and RS. No significant difference in vitreous reflectivity was detected between the former and latter patients. The finding that disease states produce significant changes in optical density ratios calls for further investigation of the possible usefulness of the parameter in differentiating between disease states, determining the outcome of various retinal diseases, and designing therapies aimed at treating the disease by correcting the abnormal density.


Poznanski D.,Tel Aviv University
Monthly Notices of the Royal Astronomical Society | Year: 2013

Three lines of evidence indicate that in the most common type of core-collapse supernovae, the energy deposited in the ejecta by the exploding core is approximately proportional to the progenitor mass cubed. This result stems from an observed uniformity of light-curve plateau duration, a correlation between mass and ejecta velocity, and the known correlation between luminosity and velocity. This result ties in analytical and numerical models together with observations, providing us with clues as to the mechanism via which the explosion of the core deposits a small fraction of its energy into the hurled envelope. © 2013 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.


Applebaum B.,Tel Aviv University
SIAM Journal on Computing | Year: 2013

We continue the study of locally computable pseudorandom generators (PRGs) G: {0, 1}n → {0, 1}m such that each of their outputs depends on a small number d of input bits. While it is known that such generators are likely to exist for the case of small sublinear stretch m = n + n1-δ, it is less clear whether achieving larger stretch such as m = n + Ω(n) or even m = n1+δ is possible. The existence of such PRGs, which was posed as an open question in previous works, has recently gained an additional motivation due to several interesting applications. We make progress towards resolving this question by obtaining several local constructions based on the onewayness of "random" local functions - a variant of an assumption made by Goldreich [Candidate one-way functions based on exporter graphs, 7 (ECCC 2000), TRCO-090]. Specifically, we construct collections of PRGs with the following parameters: (1) linear stretch m = n + Ω(n) and constant locality d = O(1); (2) polynomial stretch m = n1+δ and any (arbitrarily slowly growing) superconstant locality d = ω(1), e.g., log* n; (3) polynomial stretch m = n 1+δ, constant locality d = O(1), and inverse polynomial distinguishing advantage (as opposed to the standard case of n -ω(1)). Our constructions match the parameters achieved by previous "ad hoc" candidates and are the first to do this under a one-wayness assumption. At the core of our results lies a new search-to-decision reduction for "random" local functions. This reduction also shows that some of the previous PRG candidates can be based on one-wayness assumptions. Altogether, our results fortify the existence of local PRGs of long stretch. As an additional contribution, we show that our constructions give rise to strong inapproximability results for the densest-subgraph problem in d-uniform hypergraphs for constant d. This allows us to improve the previous bounds of Feige [Relations between average case complexity and approximation complexity, in Proceedings of STOC 2002, pp. 534-543] and Khot [Ruling out PTAS for graph min-bisection-densest subgraph and bipartate clique, in Proceedings of FOCS 2004, pp. 136-145] from constant inapproximability factor to n ε-inapproximability, at the expense of relying on stronger assumptions. © 2013 Society for Industrial and Applied Mathematics.


Hoyos C.,Tel Aviv University
International Journal of Modern Physics B | Year: 2014

Hall viscosity is a dissipationless transport coefficient whose value is quantized in units of the density in some topological phases and may be used as a measure of topological order. I give an overview of the Hall viscosity, its relation to Hall conductivity in Galilean invariant theories and its realization in effective theories. © 2014 World Scientific Publishing Company.


Shemer L.,Tel Aviv University
Natural Hazards and Earth System Science | Year: 2010

In the past decade it became customary to relate the probability of appearance of extremely steep (the so-called freak, or rogue waves) to the value of the Benjamin-Feir Index (BFI) that represents the ratio of wave nonlinearity to the spectral width. This ratio appears naturally in the cubic Schröpara;dinger equation that describes evolution of unidirectional narrow-banded wave field. The notion of this index stems from the Benjamin-Feir linear stability analysis of Stokes wave. The application of BFI to evaluate the evolution of wave fields, with non-vanishing amplitudes of sideband disturbances, is investigated using the Zakharov equation as the theoretical model. The present analysis considers a 3-wave system for which the exact analytical solution of the model equations is available. © Author(s) 2010.


We have developed a novel technique of using fluorescent tRNA for translation monitoring (FtTM). FtTM enables the identification and monitoring of active protein synthesis sites within live cells at submicron resolution through quantitative microscopy of transfected bulk uncharged tRNA, fluorescently labeled in the D-loop (fl-tRNA). The localization of fl-tRNA to active translation sites was confirmed through its co-localization with cellular factors and its dynamic alterations upon inhibition of protein synthesis. Moreover, fluorescence resonance energy transfer (FRET) signals, generated when fl-tRNAs, separately labeled as a FRET pair occupy adjacent sites on the ribosome, quantitatively reflect levels of protein synthesis in defined cellular regions. In addition, FRET signals enable detection of intra-populational variability in protein synthesis activity. We demonstrate that FtTM allows quantitative comparison of protein synthesis between different cell types, monitoring effects of antibiotics and stress agents, and characterization of changes in spatial compartmentalization of protein synthesis upon viral infection.


Avron H.,IBM | Toledo S.,Tel Aviv University
Journal of the ACM | Year: 2011

We analyze the convergence of randomized trace estimators. Starting at 1989, several algorithms have been proposed for estimating the trace of a matrix by 1/M∑ Mi=1 zTi Azi, where the zi are random vectors; different estimators use different distributions for the zis, all of which lead to E(1/M ∑Mi=1 zTi Azi) = trace(A). These algorithms are useful in applications in which there is no explicit representation of A but rather an efficient method compute z T Az given z. Existing results only analyze the variance of the different estimators. In contrast, we analyze the number of samples M required to guarantee that with probability at least 1-δ S, the relative error in the estimate is at most ε. We argue that such bounds are much more useful in applications than the variance. We found that these bounds rank the estimators differently than the variance; this suggests that minimum-variance estimators may not be the best. We also make two additional contributions to this area. The first is a specialized bound for projection matrices, whose trace (rank) needs to be computed in electronic structure calculations. The second is a new estimator that uses less randomness than all the existing estimators. © 2011 ACM.


Heyman E.,Tel Aviv University
IEEE Transactions on Antennas and Propagation | Year: 2011

We introduce two pragmatic pulsed beam (PB) expansion algorithms for radiation from a time-dependant point source, whereby the field is expanded in terms of PB propagators emerging from the source in all directions. The algorithms are based on a rigorous expansion identity involving a continuous angular spectrum of complex source pulsed beams (CSPB). The present algorithms, however, are structured upon a discrete lattice of beam directions, and utilize the iso-diffracting PB propagators (ID-PB) that may readily be tracked in non-uniform media. In the basic algorithm, the PB propagators are determined by the analytic-signal extension of the source and hence have to be re-calculated for any given source. To circumvent this difficulty we introduce a more pragmatic algorithm that utilizes time-samples of the source signal and expresses the radiated field using a set of standard-PB propagators defined by a given filter h(t). The optimal expansion parameters, namely the beam collimation, the angular spectrum discretization, the overall number of PB needed to reconstruct the field, as well as the choice of the filter h(t), are determined analytically as functions of the observation range and the excitation pulse. Guidelines for choosing these parameters are provided and are verified numerically. © 2006 IEEE.


Bar-Nun S.,Tel Aviv University | Glickman M.H.,Technion - Israel Institute of Technology
Biochimica et Biophysica Acta - Molecular Cell Research | Year: 2012

The 26S proteasome is a chambered protease in which the majority of selective cellular protein degradation takes place. Throughout evolution, access of protein substrates to chambered proteases is restricted and depends on AAA-ATPases. Mechanical force generated through cycles of ATP binding and hydrolysis is used to unfold substrates, open the gated proteolytic chamber and translocate the substrate into the active proteases within the cavity. Six distinct AAA-ATPases (Rpt1-6) at the ring base of the 19S regulatory particle of the proteasome are responsible for these three functions while interacting with the 20S catalytic chamber. Although high resolution structures of the eukaryotic 26S proteasome are not yet available, exciting recent studies shed light on the assembly of the hetero-hexameric Rpt ring and its consequent spatial arrangement, on the role of Rpt C-termini in opening the 20S 'gate', and on the contribution of each individual Rpt subunit to various cellular processes. These studies are illuminated by paradigms generated through studying PAN, the simpler homo-hexameric AAA-ATPase of the archaeal proteasome. The similarities between PAN and Rpts highlight the evolutionary conserved role of AAA-ATPase in protein degradation, whereas unique properties of divergent Rpts reflect the increased complexity and tighter regulation attributed to the eukaryotic proteasome. This article is part of a Special Issue entitled: AAA ATPases: structure and function. © 2011 Elsevier B.V.


Yeredor A.,Tel Aviv University
IEEE Transactions on Information Theory | Year: 2011

We consider the framework of Independent Component Analysis (ICA) for the case where the independent sources and their linear mixtures all reside in a Galois field of prime order P. Similarities and differences from the classical ICA framework (over the real field) are explored. We show that a necessary and sufficient identifiability condition is that none of the sources should have a uniform distribution. We also show that pairwise independence of the mixtures implies their full mutual independence (namely a nonmixing condition) in the binary (P=2) and ternary (P=3) cases, but not necessarily in higher order (P>3) cases. We propose two different iterative separation (or identification) algorithms: One is based on sequential identification of the smallest-entropy linear combinations of the mixtures and is shown to be equivariant with respect to the mixing matrix; the other is based on sequential minimization of the pairwise mutual information measures. We provide some basic performance analysis for the binary (P=2) case, supplemented by simulation results for higher orders, demonstrating advantages and disadvantages of the proposed separation approaches. © 2011 IEEE.


Segev Y.,Haifa University | Michaelson D.M.,Tel Aviv University | Rosenblum K.,Haifa University
Neurobiology of Aging | Year: 2013

Protein translation is regulated during both initiation and elongation phases to enable cells to accommodate for ever-changing environmental and internal states. Eukaryotic initiation factor-2 (eIF2)α, a major signaling pathway for responses to metabolic stress, controls translation initiation in various cells, including neurons, and affects cognitive functions. The main risk factor for sporadic Alzheimer's disease (SAD) is aging, and the main genetic risk factor reducing the age of SAD onset is the expression of apolipoprotein E (ApoE)4. We tested the hypothesis that both genetic and aging risk factors converge on the eIF2α pathway. Aged rodents showed increased eIF2α phosphorylation in the brain, indicating a shift in the rate of translation initiation with increasing age. Interestingly, mice overexpressing human ApoE4 already, at an early age, exhibited increased eIF2α phosphorylation together with mild impairment in cognitive tasks, compared with ApoE3 mice. These results suggest that the eIF2α pathway is linked to SAD, possibly via genetic as well as prolonged metabolic stress, and these findings position it as a new and important target for treatment of the currently incurable Alzheimer's disease. © 2013 Elsevier Inc.


A hallmark of neurodegenerative diseases is impairment of certain aspects of "brain functionality". Brain functionality is defined as the total input and output of the brain's neural circuits and networks. A given brain degenerative disorder does not deregulate total brain functionality but rather the activity of specific circuits in a given network, affecting their organization and topology, their cell numbers, their cellular functionality, and the interactions between neural circuits. Similarly, our concept of neurodegenerative diseases, which for many years revolved around neural survival or death, has now been extended to emphasize the role of glia. In particular, the role of glial cells in neuro-vascular communication is now known to be central to the effect of insults to the nervous system. In addition, a malfunctioning vascular system likely plays a role in the etiology of certain neurodegenerative diseases. Thus, the symptoms of neurodegenerative or more correctly brain degenerative disease are, to a very large extent, a result of impairment in glial cells that lead to pathological neuro-vascular interactions that, in turn, generate a rather "hostile" environment in which the neurons fail to function. These events lead to systematic neural cell death on a scale that appears to be proportional to the severity of the neurological deficit. © 2013 Elsevier B.V.


Toch E.,Tel Aviv University
Personal and Ubiquitous Computing | Year: 2014

Developers of context-aware applications are faced with a tough challenge: powerful privacy controls are essential to maintain user trust, but they are also hard to use and not adequate in all situations. To address this tradeoff, we present Super-Ego, a crowdsourcing framework for privacy management of location information in ubiquitous environment. We study how crowdsourcing can be used to predict the user's privacy preferences for different location on the basis of the general user population. The crowdsourcing methods are evaluated in a 2-week user study in which we tracked the locations of 30 subjects and asked them to provide privacy preferences for the locations they had visited. Our results show that by employing simple methods for semantic analysis of locations and by profiling the user's privacy inclination, our methods can accurately predict the privacy preferences for 80 % of the user's locations. By employing semi-automatic decision strategies, which ask the user to decide regarding the privacy of some of the locations, the accuracy rate raises to 90 %. © 2012 Springer-Verlag London.


Shaked N.T.,Tel Aviv University
Optics Letters | Year: 2012

This Letter presents the τ interferometer, a portable and inexpensive device for obtaining spatial interferograms of microscopic biological samples without the strict stability and the highly coherent illumination that are usually required for interferometric microscopy setups. The device is built using off-the-shelf optical elements and can easily operate with low-coherence illumination, while being positioned in the output of a conventional inverted microscope. The interferograms are processed into the quantitative amplitude and phase profiles of the sample. Based on the phase profile, the optical-path-delay profile is obtained with temporal stability of 0.18 nm and spatial stability of 0.42 nm. Further experimental demonstration of using the τ interferometer for imaging the quantitative thickness profile of a live red blood cell is provided. © 2012 Optical Society of America.


Gileadi E.,Tel Aviv University
Journal of Solid State Electrochemistry | Year: 2011

A critical view of interfacial electrochemistry in the past 50 years is discussed, with emphasis on tacit assumptions, which are sometimes hard to justify. The important role of the Tafel equation in studies of the mechanism of electrode reactions and in the development of electrode kinetics in the past century is recognized. However, it is shown that the validity of the ways it was implemented can be questioned, particularly in view of the uncertainty in the value of the symmetry factor commonly assumed. For example, the value of ? pertinent to a species in the outer-Helmholtz plane cannot be the same as that applicable to a species already adsorbed on the surface. Three factors are involved in considering charge transfer to an adsorbed species: (a) The electrostatic field at the adsorption site is highly distorted; thus, the overpotential imposed may not apply at the point where the reaction takes place; (b) the effective charge on the adsorbed species may not equal the nominal charge assigned to it; and (c) the metal surface may already be modified by a monolayer of adsorbed species of the same kind, which is, however, inactive with respect to the reaction taking place. Similarly, in studies of the kinetics of metal deposition and dissolution, where charge is transferred across the interface by the ions, one cannot legitimately assume a value of ?, although it can be measured experimentally. It is very risky to predict the future of interfacial electrochemistry, but one might extrapolate present trends. Thus, the importance of the fundamental aspects of the field may have declined in the past two or three decades, and this trend will probably continue. On the other hand, the importance of understanding interfacial electrochemistry as a basis for related fields such as nano-science, biology, micro-and nano-implanted biosensors, interaction of tissue with metal implants, materials science, as well as technologies such as corrosion and alloy plating is likely to increase. © 2011 Springer-Verlag.


Sukharev M.,Arizona State University | Nitzan A.,Tel Aviv University
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2011

We consider the interaction of electromagnetic radiation of arbitrary polarization with multilevel atoms in a self-consistent manner, taking into account both spatial and temporal dependencies of local fields. This is done by numerically solving the corresponding system of coupled Maxwell-Liouville equations for various geometries. In particular, we scrutinize linear optical properties of nanoscale atomic clusters, demonstrating the significant role played by collective effects and dephasing. It is shown that subwavelength atomic clusters exhibit two resonant modes, one of which is localized slightly below the atomic transition frequency of an individual atom, while the other is positioned considerably above it. As an initial exploration of future applications of this approach, the optical response of core-shell nanostructures, with a core consisting of silver and a shell composed of resonant atoms, is examined. © 2011 American Physical Society.


Matz H.,Tel Aviv University
Clinics in Dermatology | Year: 2010

In dermatologic practice, phototherapy is restricted mainly to the use of ultraviolet radiation. When used in combination with a photosensitizing chemical, it becomes photochemotherapy. Discussion of these therapeutic modalities includes mode of use, indications, and unwanted effects. © 2010.


Sheppes G.,Tel Aviv University | Suri G.,Stanford University | Gross J.J.,Stanford University
Annual Review of Clinical Psychology | Year: 2015

Emotional problems figure prominently in many clinical conditions. Recent efforts to explain and treat these conditions have emphasized the role of emotion dysregulation. However, emotional problems are not always the result of emotion dysregulation, and even when emotional problems do arise from emotion dysregulation, it is necessary to specify precisely what type of emotion dysregulation might be operative. In this review, we present an extended process model of emotion regulation, and we use this model to describe key points at which emotion-regulation difficulties can lead to various forms of psychopathology. These difficulties are associated with (a) identification of the need to regulate emotions, (b) selection among available regulatory options, (c) implementation of a selected regulatory tactic, and (d) monitoring of implemented emotion regulation across time. Implications and future directions for basic research, assessment, and intervention are discussed. © 2015 by Annual Reviews. All rights reserved.


Goldbourt A.,Tel Aviv University
Current Opinion in Biotechnology | Year: 2013

The link of structure and dynamics of biomolecules and their complexes to their function and to many cellular processes has driven the quest for their detailed characterization by a variety of biophysical techniques. Magic-angle spinning solid-state nuclear magnetic resonance spectroscopy provides detailed information on the structural properties of such systems and in particular contributes invaluable information on non-soluble, large molecular-weight and non-crystalline biomolecules. This review summarizes the recent progress that has been made in the characterization of macromolecular assemblies, viruses, membrane proteins, amyloid fibrils, protein aggregates and more by magic-angle spinning solid-state NMR. © 2013 Elsevier Ltd.


Werner H.,Tel Aviv University | LeRoith D.,Clinical Research Institute at Rambam LHCRIR
European Neuropsychopharmacology | Year: 2014

The involvement of insulin, the insulin-like growth factors (IGF1, IGF2) and their receptors in central nervous system development and function has been the focus of scientific interest for more than 30 years. The insulin-like peptides, both locally-produced proteins as well as those transported from the circulation into the brain via the blood-brain barrier, are involved in a myriad of biological activities. These actions include, among others, neuronal survival, neurogenes, angiogenesis, excitatory and inhibitory neurotransmission, regulation of food intake, and cognition. In recent years, a linkage between brain insulin/IGF1 and certain neuropathologies has been identified. Epidemiological studies have demonstrated a correlation between diabetes (mainly type 2) and Alzheimer's disease. In addition, an aberrant decline in IGF1 values was suggested to play a role in the development of Alzheimer's disease. The present review focuses on the expression and function of insulin, IGFs and their receptors in the brain in physiological and pathological conditions. © 2014 Elsevier B.V. and ECNP.


Cohen Y.,Tel Aviv University
International Journal of Production Research | Year: 2012

This paper analyses the effects of absenteeism in assembly lines. The analysis shows that assigning temporary workers as substitutes for absentees has a major potential for generating bottlenecks. Such a bottleneck typically appears when an inexperienced worker replaces an absentee worker at their position. The inexperienced worker starts their learning curve, and for the initial period is significantly slower than other stations, and therefore is a bottleneck. The paper analyses the effect of typical absenteeism rates on the throughput, and shows it has strategic magnitude. This is verified using simulation. The effect of the absenteeism and turnover on the throughput is found to be related to the cycle time, and the amount and rate of learning. The paper discusses the simulation results, staffing requirements, strategies for overcoming absenteeism, and future research directions. © 2012 Copyright Taylor and Francis Group, LLC.


The categorization of individuals as "male" or "female" is based on chromosome complement and gonadal and genital phenotype. This combined genetic-gonadal-genitals sex, here referred to as 3G-sex, is internally consistent in ~99% of humans (i.e., one has either the "female" form at all levels, or the "male" form at all levels). About 1% of the human population is identified as "intersex" because of either having an intermediate form at one or more levels, or having the "male" form at some levels and the "female" form at other levels. These two types of "intersex" reflect the facts, respectively, that the different levels of 3G-sex are not completely dimorphic nor perfectly consistent. Using 3G-sex as a model to understand sex differences in other domains (e.g., brain, behavior) leads to the erroneous assumption that sex differences in these other domains are also highly dimorphic and highly consistent. But parallel lines of research have led to the conclusion that sex differences in the brain and in behavior, cognition, personality, and other gender characteristics are for the most part not dimorphic and not internally consistent (i.e., having one brain/gender characteristic with the "male" form is not a reliable predictor for the form of other brain/gender characteristics). Therefore although only ~1% percent of humans are 3G-"intersex", when it comes to brain and gender, we all have an intersex gender (i.e., an array of masculine and feminine traits) and an intersex brain (a mosaic of "male" and "female" brain characteristics). © 2012 Joel; licensee BioMed Central Ltd.


Gefen A.,Tel Aviv University
Journal of Tissue Viability | Year: 2010

Heel ulcers are common, dangerous and costly, but their etiology is poorly understood and no biomechanical studies were conducted to explore it. This paper describes a biomechanical investigation of heel ulcers using a theoretical model that characterizes the internal mechanical loading at the soft tissues of a supported heel. The study is aimed first at identifying some heel-ulcer-specific risk factors pointed out by the biomechanical theory, and second, at demonstrating the kind of support that biomechanical theory and computer modeling can offer in the conduct of clinical studies in the pressure ulcer field. The modeling demonstrated that atypical foot anatomies characterized by heavy-weight foot, sharp posterior calcaneus and thin soft tissue padding are theoretically more prone to heel ulcers. Diabetes and edema at the feet were also predicted to impose risks for heel ulcers, which agrees very well with clinical observations. This paper therefore demonstrated that a biomechanical theory can be used to explain and interpret clinical and epidemiological findings related to heel ulcers. ©2010 Tissue Viability Society.


Shoenfeld Y.,Tel Aviv University
Clinical Reviews in Allergy and Immunology | Year: 2013

It is astounding to consider that virtually, every textbook of physiology in every medical school in the world does not include a chapter on immunology. On the other hand, virtually, in every textbook in internal medicine, immunology and immune response overlaps with every tissue and every organ. Indeed, historically, the concept of the immune response was recognized primarily in the setting of allergy and/or anaphylaxis. Indeed, the very concepts of infection, microbiology and host protection are relatively new sciences. In fact, it was little more than 100 years ago when washing hands became what is now coined standard of care. How different it is in 2013, where one finds Handi Wipes for shoppers to use at grocery stores to protect themselves from the flora on shopping cart handles. Autoimmunity is even a newer concept without going into the well-known history of Paul Ehrlich and hemolytic anemias, the LE cell, and the beginning field of serology (and rheumatoid factor discovery). It is apparent that our understanding of autoimmunity has become linked hand-in-glove with new tools and investigational probes into serology and, more recently, the cellular immune response. With such discoveries, a number of key observations stand out. Firstly, there are a great deal more autoantibodies than there are autoimmune diseases. Second, there are a great deal more of autoimmune diseases than was believed in 1963 on the occasion of the publication of the first textbook of autoimmune diseases. Third, autoimmune diseases are, for the most part, orphan diseases, with many entities afflicting too few patients to excite the financial limb of pharmaceutical companies. In this special issue, we have grouped a number of papers, many of which were presented at the recent Congress of Autoimmunity that focus on issues that are not commonly discussed in autoimmunity. It reminds us that due to the ubiquitous nature of the innate and adaptive response, that there are a large number of diseases that have either an inflammatory and/or specific autoimmune response, we have to keep an open eye because everything is potentially autoimmune until proven otherwise. © 2013 Springer Science+Business Media New York.


Barkay Z.,Tel Aviv University
Applied Physics Letters | Year: 2010

A method for quantitative wettability study at nanoscale is presented. It is based on measuring transmitted electrons through nanodroplets using wet scanning transmission electron microscope (wet-STEM) detector in environmental scanning electron microscope. The quantitative information of the nanodroplet shape and contact angle is obtained by fitting Monte Carlo simulation results for transmitted electrons through spherical cap geometry with the experimental wet-STEM results. The characterization is demonstrated for particles and for initial stages of water droplet condensation over a nonhomogeneous holey carbon grid. The method is suggested for application in thin polymer and biological films. © 2010 American Institute of Physics.


Deutscher G.,Tel Aviv University
Applied Physics Letters | Year: 2010

Superconducting cuprates and pnictides composed of CuO2 or AsFe planes, respectively, with intercalated insulating layers, are at the crossroads of three families of crystalline solids: Metals, doped Mott insulators, and ferroelectrics. The metallic and doped insulator approaches to high temperature superconductivity are essentially electronic ones, while in ferroelectrics atomic displacements play a key role. We show that pairing by contraction of in-plane Cu-O (or As-Fe) bonds, as proposed by the bond contraction pairing model, is prevented by the tensile strain generated by dislocations at grain boundaries. This explains why weak link behavior already sets in at low angle boundaries. © 2010 American Institute of Physics.


Galperin M.,University of California at San Diego | Nitzan A.,Tel Aviv University
Journal of Physical Chemistry Letters | Year: 2011

Surface-enhanced Raman scattering (SERS) was recently used to monitor nonequilibrium properties of molecular conduction junctions. Ward et al. (Nat. Nanotechnol. 2011, 6, 33) have used such measurements to estimate heating of the molecular vibrations (indicated by the ratio between Stokes and anti-Stokes Raman peaks) as well as the electronic metal substrate (inferred from the corresponding components of the Raman continuum). The latter observation suggests, contrary to standard assumptions, significant heating of the metal contacts. Here, we discuss this observation by advancing a theory of the electronic Raman scattering background in biased current carrying molecular junctions and using it to estimate the electronic heating, as seen in the Raman signal. We reach the unexpected conclusion that while heating of the electronic background in Raman scattering from biased molecular junctions is indeed observed, this does not necessarily imply an appreciable deviation from thermal equilibrium in the electronic distributions in the leads. © 2011 American Chemical Society.


Efremenko K.,Tel Aviv University
SIAM Journal on Computing | Year: 2012

Locally decodable codes (LDCs) allow one to decode any particular symbol of the input message by making a constant number of queries to a codeword, even if a constant fraction of the codeword is damaged. In a recent work [J. ACM, 55(2008), article 1], Yekhanin constructs a 3-query LDC with subexponential length. However, this construction requires a conjecture that there are infinitely many Mersenne primes. In this paper, we give the first unconditional constant query LDC construction with subexponential codeword length. In addition, our construction reduces codeword length. Copyright © by SIAM.


Beilis I.I.,Tel Aviv University
Applied Physics Letters | Year: 2010

Generally the gap voltage at the moment of arc initiation in a vacuum is significantly larger than the voltage in developed arcs. This phenomenon was studied here suggesting a physical model for initially triggered at the bulk cathode plasma and then for appeared transient spot. The model allows calculating the transient energy flux to the cathode and the transient cathode potential drop (CPD). It was shown that the CPD at the moment of spot ignition is relatively large and significantly contributes to the arc voltage at arc ignition. The subsequent voltage decrease can be understood from the transient CPD behavior during arc development. The voltage oscillation in an arc was explained by suggested model taking into account the spot shifting on a cold location. © 2010 American Institute of Physics.


Bar-Eli K.,Tel Aviv University
Physical Chemistry Chemical Physics | Year: 2011

The coupling of identical reactors containing chemical oscillators is discussed. The coupling is executed by means of transferring chemical species from one cell (reactor) to the other in a diffusion like manner i.e. in proportion to the concentration difference between the cells. The coupling rate constant, however, is the same for all species. The individual, uncoupled, cells may be oscillating or in a stable steady state (the same for all reactors). In both cases, depending on the initial conditions, the symmetry breaks, and the cells may end upcontrary to intuitionin a stable steady state in which the final concentrations are not equal in the various reactors. The Brusselator and Oregonator mechanisms are examined and they behave in the manner described. On the other hand, the Lotka-Volterra mechanism, being conservative, keeps, when coupled, only the homogeneous solutions. © 2011 the Owner Societies.


Barone V.,Central Michigan University | Hod O.,Tel Aviv University | Peralta J.E.,Central Michigan University | Scuseria G.E.,Rice University
Accounts of Chemical Research | Year: 2011

Over the last several years, low-dimensional graphene derivatives, such as carbon nanotubes and graphene nanoribbons, have played a central role in the pursuit of a plausible carbon-based nanotechnology. Their electronic properties can be either metallic or semiconducting depending purely on morphology, but predicting their electronic behavior has proven challenging. The combination of experimental efforts with modeling of these nanometer-scale structures has been instrumental in gaining insight into their physical and chemical properties and the processes involved at these scales. Particularly, approximations based on density functional theory have emerged as a successful computational tool for predicting the electronic structure of these materials. In this Account, we review our efforts in modeling graphitic nanostructures from first principles with hybrid density functionals, namely the Heyd-Scuseria-Ernzerhof (HSE) screened exchange hybrid and the hybrid meta-generalized functional of Tao, Perdew, Staroverov, and Scuseria (TPSSh).These functionals provide a powerful tool for quantitatively studying structure-property relations and the effects of external perturbations such as chemical substitutions, electric and magnetic fields, and mechanical deformations on the electronic and magnetic properties of these low-dimensional carbon materials. We show how HSE and TPSSh successfully predict the electronic properties of these materials, providing a good description of their band structure and density of states, their work function, and their magnetic ordering in the cases in which magnetism arises. Moreover, these approximations are capable of successfully predicting optical transitions (first and higher order) in both metallic and semiconducting single-walled carbon nanotubes of various chiralities and diameters with impressive accuracy. This versatility includes the correct prediction of the trigonal warping splitting in metallic nanotubes.The results predicted by HSE and TPSSh provide excellent agreement with existing photoluminescence and Rayleigh scattering spectroscopy experiments and Green's function-based methods for carbon nanotubes. This same methodology was utilized to predict the properties of other carbon nanomaterials, such as graphene nanoribbons. Graphene nanoribbons may be viewed as unrolled (and passivated) carbon nanotubes. However, the emergence of edges has a crucial impact on the electronic properties of graphene nanoribbons. Our calculations have shown that armchair nanoribbons are predicted to be nonmagnetic semiconductors with a band gap that oscillates with their width. In contrast, zigzag graphene nanoribbons are semiconducting with an electronic ground state that exhibits spin polarization localized at the edges of the carbon nanoribbon. The spatial symmetry of these magnetic states in graphene nanoribbons can give rise to a half-metallic behavior when a transverse external electric field is applied. Our work shows that these properties are enhanced upon different types of oxidation of the edges. We also discuss the properties of rectangular graphene flakes, which present spin polarization localized at the zigzag edges. © 2011 American Chemical Society.


Nissan J.,Tel Aviv University
The International journal of oral & maxillofacial implants | Year: 2011

The present study was designed to compare the long-term outcome and complications of cemented versus screw-retained implant restorations in partially edentulous patients. Consecutive patients with bilateral partial posterior edentulism comprised the study group. Implants were placed, and cemented or screw-retained restorations were randomly assigned to the patients in a split-mouth design. Follow-up (up to 15 years) examinations were performed every 6 months in the first year and every 12 months in subsequent years. The following parameters were evaluated and recorded at each recall appointment: ceramic fracture, abutment screw loosening, metal frame fracture, Gingival Index, and marginal bone loss. Thirty-eight patients were treated with 221 implants to support partial prostheses. No implants during the follow-up period (mean follow-up, 66 ± 47 months for screw-retained restorations [range, 18 to 180 months] and 61 ± 40 months for cemented restorations [range, 18 to 159 months]). Ceramic fracture occurred significantly more frequently (P < .001) in screw-retained (38% ± 0.3%) than in cemented (4% ± 0.1%) restorations. Abutment screw loosening occurred statistically significantly more often (P = .001) in screw-retained (32% ± 0.3%) than in cement-retained (9% ± 0.2%) restorations. There were no metal frame fractures in either type of restoration. The mean Gingival Index scores were statistically significantly higher (P < .001) for screw-retained (0.48 ± 0.5) than for cemented (0.09 ± 0.3) restorations. The mean marginal bone loss was statistically significantly higher (P < .001) for screw-retained (1.4 ± 0.6 mm) than for cemented (0.69 ± 0.5 mm) restorations. The long-term outcome of cemented implant-supported restorations was superior to that of screw-retained restorations, both clinically and biologically.


There are no clear recommended imaging guidelines for the assessment of patients presenting primarily with obstructed defecation syndrome and defecation difficulty. The gold standard has always been the defecating proctogram which may require a rather poorly tolerated extended technique involving high-radiation exposure in young women which includes cystography, vaginography, small bowel opacification, and occasional peritoneography. The development of dynamic magnetic resonance imaging has obviated many of these extended techniques and may be supplemented by novel ultrasonographic methods including dynamic transperineal sonography, real-time 3D translabial ultrasound and 3D dynamic echodefecography. Patients potentially suitable for surgical treatment display a multiplicity of pelvic floor and perineal soft-tissue anomalies where one pathology (such as rectocele or enterocele) are considered dominant. Despite the introduction of recent stapled and robotic technologies, there is a dual dialog concerning the functional outcome of these procedures. Imaging and surgical algorithms for these patients are provided. © 2012 Springer Science+Business Media, LLC.


Katzav E.,Kings College London | Schwartz M.,Tel Aviv University
Physical Review Letters | Year: 2011

In this Letter, we derive exponent inequalities relating the dynamic exponent z to the steady state exponent Γ for a general class of stochastically driven dynamical systems. We begin by deriving a general exact inequality, relating the response function and the correlation function, from which the various exponent inequalities emanate. We then distinguish between two classes of dynamical systems and obtain different and complementary inequalities relating z and Γ. The consequences of those inequalities for a wide set of dynamical problems, including critical dynamics and Kardar-Parisi-Zhang-like problems, are discussed. © 2011 American Physical Society.


Selzer Y.,Tel Aviv University | Peskin U.,Technion - Israel Institute of Technology
Journal of Physical Chemistry C | Year: 2013

Molecular electronic devices are a promising future alternative to standard electronic switches due to their fast response on the pico-second time scale. An experimental scheme is proposed in order to correlate pico-second dynamics in molecular junctions to steady state current measurements. The time resolution is obtained using a sequence of ultrafast pulse pair excitations with a controlled time delay between the two pulses in each pair. The dependence of the steady state current on the delay time reveals the periods of molecular dynamics on the sub-pico-second time scale. The approach is demonstrated theoretically for a generic model of a single molecule based coherent electron pump. Theoretical analysis enables to correlate the steady state current to the underlying intramolecular dynamics. © 2013 American Chemical Society.


Efros A.,Tel Aviv University
BMC bioinformatics | Year: 2012

Haplotype phasing is a well studied problem in the context of genotype data. With the recent developments in high-throughput sequencing, new algorithms are needed for haplotype phasing, when the number of samples sequenced is low and when the sequencing coverage is blow. High-throughput sequencing technologies enables new possibilities for the inference of haplotypes. Since each read is originated from a single chromosome, all the variant sites it covers must derive from the same haplotype. Moreover, the sequencing process yields much higher SNP density than previous methods, resulting in a higher correlation between neighboring SNPs. We offer a new approach for haplotype phasing, which leverages on these two properties. Our suggested algorithm, called Perfect Phlogeny Haplotypes from Sequencing (PPHS) uses a perfect phylogeny model and it models the sequencing errors explicitly. We evaluated our method on real and simulated data, and we demonstrate that the algorithm outperforms previous methods when the sequencing error rate is high or when coverage is low.


Rozov R.,Tel Aviv University
BMC bioinformatics | Year: 2012

RNA-Seq is a technique that uses Next Generation Sequencing to identify transcripts and estimate transcription levels. When applying this technique for quantification, one must contend with reads that align to multiple positions in the genome (multireads). Previous efforts to resolve multireads have shown that RNA-Seq expression estimation can be improved using probabilistic allocation of reads to genes. These methods use a probabilistic generative model for data generation and resolve ambiguity using likelihood-based approaches. In many instances, RNA-seq experiments are performed in the context of a population. The generative models of current methods do not take into account such population information, and it is an open question whether this information can improve quantification of the individual samples In order to explore the contribution of population level information in RNA-seq quantification, we apply a hierarchical probabilistic generative model, which assumes that expression levels of different individuals are sampled from a Dirichlet distribution with parameters specific to the population, and reads are sampled from the distribution of expression levels. We introduce an optimization procedure for the estimation of the model parameters, and use HapMap data and simulated data to demonstrate that the model yields a significant improvement in the accuracy of expression levels of paralogous genes. We provide a proof of principal of the benefit of drawing on population commonalities to estimate expression. The results of our experiments demonstrate this approach can be beneficial, primarily for estimation at the gene level.


Liu K.,KTH Royal Institute of Technology | Fridman E.,Tel Aviv University
Systems and Control Letters | Year: 2014

This paper deals with the solution bounds for time-delay systems via delay-dependent Lyapunov-Krasovskii methods. Solution bounds are widely used for systems with input saturation caused by actuator saturation or by the quantizers with saturation. We show that an additional bound for solutions is needed for the first time-interval, where t<τ(t), both in the continuous and in the discrete time. This first time-interval does not influence on the stability and the exponential decay rate analysis. The analysis of the first time-interval is important for nonlinear systems, e.g., for finding the domain of attraction. Regional stabilization of a linear (probably, uncertain) system with unknown and bounded input delay under actuator saturation is revisited, where the saturation avoidance approach is used. © 2013 Elsevier B.V. All rights reserved.


Reich Y.,Tel Aviv University
Research in Engineering Design | Year: 2013

Design science is concerned with the study, investigation and accumulation of knowledge about the design process and its constituent operations. It aims to collect, organize and improve those aspects of thought and information which are available concerning design, and to specify and carry out research in those areas of design which are likely to be of value to practical designers and design organizations. Technical knowledge presented in a new order, totality and form then becomes a striking and productive tool for designers. Essential positive effects are to be expected in a relatively short time in engineering education, and through suitable derivations and adjustments of this science for particular purposes. Clearly design goes deeper into the sciences as the means to devise all the instruments for collecting data. In fact, there are discoveries such as the Higgs boson particle or far away stars that are solely based on measured traces that are used in calculations and interpreted as discoveries of never-to-be-seen objects.


Shayevitz O.,University of California at San Diego | Feder M.,Tel Aviv University
IEEE Transactions on Information Theory | Year: 2011

In this paper, we introduce a fundamental principle for optimal communication over general memoryless channels in the presence of noiseless feedback, termed posterior matching. Using this principle, we devise a (simple, sequential) generic feedback transmission scheme suitable for a large class of memoryless channels and input distributions, achieving any rate below the corresponding mutual information. This provides a unified framework for optimal feedback communication in which the Horstein scheme (BSC) and the Schalkwijk-Kailath scheme (AWGN channel) are special cases. Thus, as a corollary, we prove that the Horstein scheme indeed attains the BSC capacity, settling a longstanding conjecture. We further provide closed form expressions for the error probability of the scheme over a range of rates, and derive the achievable rates in a mismatch setting where the scheme is designed according to the wrong channel model. Several illustrative examples of the posterior matching scheme for specific channels are given, and the corresponding error probability expressions are evaluated. The proof techniques employed utilize novel relations between information rates and contraction properties of iterated function systems. © 2011 IEEE.


Guo P.,Hong Kong Polytechnic University | Hassin R.,Tel Aviv University
Operations Research | Year: 2011

We consider a single server queueing system in which service shuts down when there are no customers present and is resumed only when the queue length reaches a given critical length. We analyze the strategic response of customers to this mechanism and compare it to the overall optimal behavior, with and without information on delay. The results are significantly different from those obtained when the server is continuously available. We show that there may exist multiple equilibria in such a system and the optimal arrival rate may be greater or smaller than that of the decentralized equilibrium. Finally, the critical length is taken as a decision variable, and the optimal operations policy is discussed by taking strategic customers into consideration. © 2011 INFORMS.


Nussinov R.,Frederick National Laboratory for Cancer Research | Nussinov R.,Tel Aviv University | Tsai C.-J.,Frederick National Laboratory for Cancer Research
Cell | Year: 2013

Allostery is largely associated with conformational and functional transitions in individual proteins. This concept can be extended to consider the impact of conformational perturbations on cellular function and disease states. Here, we clarify the concept of allostery and how it controls physiological activities. We focus on the challenging questions of how allostery can both cause disease and contribute to development of new therapeutics. We aim to increase the awareness of the linkage between disease symptoms on the cellular level and specific aberrant allosteric actions on the molecular level and to emphasize the potential of allosteric drugs in innovative therapies. © 2013 Elsevier Inc.


Dubi Y.,Los Alamos National Laboratory | Dubi Y.,Tel Aviv University | Balatsky A.V.,Los Alamos National Laboratory
Physical Review Letters | Year: 2011

A phenomenological model for the "hidden order" transition in the heavy-Fermion material URu2Si2 is introduced. The hidden order is identified as an incommensurate, momentum-carrying hybridization between the light hole band and the heavy electron band. This modulated hybridization appears after a Fano hybridization at higher temperatures takes place. We focus on the hybridization wave as the order parameter in URu 2Si2 and possibly other materials with similar band structures. The model is qualitatively consistent with numerous experimental results obtained from, e.g., neutron scattering and scanning tunneling microscopy. Specifically, we find a gaplike feature in the density of states and the appearance of features at an incommensurate vector Q *∼0.6π/a0. Finally, the model allows us to make various predictions which are amenable to current experiments. © 2011 American Physical Society.


Kol U.,Tel Aviv University
Journal of High Energy Physics | Year: 2014

We study the dual 3d Euclidean RG flow of single-field slow-roll Inflation using the postulates of the dS/CFT correspondence. For that purpose we solve for the inflationary fluctuation at all times using a matching procedure between two approximate solutions which are separately valid at different regions of the space of parameters but together cover all of it. The two modes of the full solution mix such that each of the modes at late times is a superposition of the modes in the quasi-de Sitter region. We find that the dual theory admits two phases of explicit and spontaneous breaking of conformal symmetry. We also find that the mixing effect between the two modes in the bulk implies that slow-roll inflation does not guarantee, but rather generically generates, a nearly scale invariant power spectrum, except in fine-tuned situations. We suggest that the mixing effect can have a unique signature on other cosmological observables such as the bispectrum. © 2014 SISSA.


Yurovsky V.A.,Tel Aviv University | Yurovsky V.A.,University of California at Santa Barbara
Physical Review Letters | Year: 2014

Many-body systems of identical arbitrary-spin particles, with separable spin and spatial degrees of freedom, are considered. Their eigenstates can be classified by Young diagrams, corresponding to nontrivial permutation symmetries (beyond the conventional paradigm of symmetric-antisymmetric states). The present work obtains the following. (a) Selection rules for additional nonseparable (dependent on spins and coordinates) k-body interactions: the Young diagrams, associated with the initial and final states of a transition, can differ by relocation of no more than k boxes between their rows. (b) Correlation rules in which eigenstate-averaged local correlations of k particles vanish if k exceeds the number of columns (for bosons) or rows (for fermions) in the associated Young diagram. It also elucidates the physical meaning of the quantities conserved due to permutation symmetry - in 1929, Dirac identified those with characters of the symmetric group - relating them to experimentally observable correlations of several particles. The results provide a way to control the formation of entangled states belonging to multidimensional non-Abelian representations of the symmetric group. These states can find applications in quantum computation and metrology. © 2014 American Physical Society.


Driben R.,Tel Aviv University | Babushkin I.,Weierstrass Institute for Applied Analysis And Stochastics
Optics Letters | Year: 2012

Soliton fusion is a fascinating and delicate phenomenon that manifests itself in optical fibers in case of interaction between copropagating solitons with small temporal and wavelength separation. We show that the mechanism of acceleration of a trailing soliton by dispersive waves radiated from the preceding one provides necessary conditions for soliton fusion at the advanced stage of supercontinuum generation in photonic-crystal fibers. As a result of fusion, large-intensity robust light structures arise and propagate over significant distances. In the presence of small random noise the delicate condition for the effective fusion between solitons can easily be broken, making the fusion-induced giant waves a rare statistical event. Thus oblong-shaped giant accelerated waves become excellent candidates for optical rogue waves. © 2012 Optical Society of America.


Liu J.,Frederick National Laboratory for Cancer Research | Nussinov R.,Frederick National Laboratory for Cancer Research | Nussinov R.,Tel Aviv University
Critical Reviews in Biochemistry and Molecular Biology | Year: 2013

The ubiquitin-proteasome system (UPS) is involved in many cellular processes including protein degradation. Degradation of a protein via this system involves two successive steps: ubiquitination and degradation. Ubiquitination tags the target protein with ubiquitin-like proteins (UBLs), such as ubiquitin, small ubiquitin-like modifier (SUMO) and NEDD8, via a cascade involving three enzymes: activating enzyme E1, conjugating enzyme E2 and E3 ubiquitin ligases. The proteasomes recognize the UBL-tagged substrate proteins and degrade them. Accumulating evidence indicates that allostery is a central player in the regulation of ubiquitination, as well as deubiquitination and degradation. Here, we provide an overview of the key mechanistic roles played by allostery in all steps of these processes, and highlight allosteric drugs targeting them. Throughout the review, we emphasize the crucial mechanistic role played by linkers in allosterically controlling the UPS action by biasing the sampling of the conformational space, which facilitate the catalytic reactions of the ubiquitination and degradation. Finally, we propose that allostery may similarly play key roles in the regulation of molecular machines in the cell, and as such allosteric drugs can be expected to be increasingly exploited in therapeutic regimes. © 2013 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.


S-acylation, also known as palmitoylation, involves the attachment of acyl fatty acids to thiol groups of cysteine residues through a reversible thioester bond. Owing to its reversibility, S-acylation is important in regulation of diverse signaling cascades, including Ras-associated cancers in mammals, stress response and metabolic regulation. Here we describe a simple protocol for analysis of protein S-acylation using gas chromatography-coupled mass spectrometry. Analysis can be carried out with as little as 1 microg of purified protein and allows chemical identification and, potentially, quantification of the acyl moieties. The method is based on cleavage of the fatty acids from proteins by hydrogenation with platinum (IV) oxide. This causes an acid transesterification of the acyl groups, adding an ethyl group to the carboxyl head of the fatty acid. The addition of the ethyl group reduces the polarity of the fatty acids, allowing their efficient separation by gas chromatography.


Siegman-Igra Y.,Tel Aviv University
Scandinavian Journal of Infectious Diseases | Year: 2010

In the 2007 American Heart Association guidelines, gastrointestinal (GI) and genitourinary (GU) procedures were removed from the indications for infective endocarditis (IE) prophylaxis. The purpose of this study was to estimate the contribution of GI and GU procedures to the occurrence of IE in order to appreciate whether this removal was justified. Among 212 episodes of IE prospectively collected during 7 y, 20 cases (9%) had invasive GI and GU procedures and 17 (8%) had dental interventions within 3 months before IE diagnosis. Enteric organisms (predominantly Enterococcus faecalis) were significantly more common in the GI and GU group than in all other patients, whereas viridans streptococci, the most common pathogen in the dental group, were absent from the GI and GU group. This unique combination of pathogens in the GI and GU group is highly suggestive of a true association between the procedure and IE. Hence, GI and GU procedures pose a non-negligible risk of acquisition of IE. Consequently, it is proposed here, that adults at high risk of IE who undergo surgical GI and GU procedures, receive prophylaxis that includes an anti-enterococcal agent. © Informa UK Ltd. 2010.


Kronfeld-Schor N.,Tel Aviv University
Proceedings. Biological sciences / The Royal Society | Year: 2013

Most studies in chronobiology focus on solar cycles (daily and annual). Moonlight and the lunar cycle received considerably less attention by chronobiologists. An exception are rhythms in intertidal species. Terrestrial ecologists long ago acknowledged the effects of moonlight on predation success, and consequently on predation risk, foraging behaviour and habitat use, while marine biologists have focused more on the behaviour and mainly on reproduction synchronization with relation to the Moon phase. Lately, several studies in different animal taxa addressed the role of moonlight in determining activity and studied the underlying mechanisms. In this paper, we review the ecological and behavioural evidence showing the effect of moonlight on activity, discuss the adaptive value of these changes, and describe possible mechanisms underlying this effect. We will also refer to other sources of night-time light ('light pollution') and highlight open questions that demand further studies.


Ovarian carcinoma is the fifth common cause of cancer death in women, despite advanced therapeutic approaches. αvβ3 integrin, a plasma membrane receptor, binds thyroid hormones (L-thyroxine, T4; 3,5,3’-triiodo-L-thyronine, T3) and is overexpressed in ovarian cancer. We have demonstrated selective binding of fluorescently labeled hormones to αvβ3-positive ovarian cancer cells but not to integrin-negative cells. Physiologically relevant T3 (1 nM) and T4 (100 nM) concentrations in OVCAR-3 (high αvβ3) and A2780 (low αvβ3) cells promoted αv and β3 transcription in association with basal integrin levels. This transcription was effectively blocked by RGD (Arg–Gly–Asp) peptide and neutralizing αvβ3 antibodies, excluding T3-induced β3 messenger RNA, suggesting subspecialization of T3 and T4 binding to the integrin receptor pocket. We have provided support for extracellular regulated kinase (ERK)-mediated transcriptional regulation of the αv monomer by T3 and of β3 monomer by both hormones and documented a rapid (30–120 min) and dose-dependent (0.1–1000 nM) ERK activation. OVCAR-3 cells and αvβ3-deficient HEK293 cells treated with αvβ3 blockers confirmed the requirement for an intact thyroid hormone-integrin interaction in ERK activation. In addition, novel data indicated that T4, but not T3, controls integrin's outside-in signaling by phosphorylating tyrosine 759 in the β3 subunit. Both hormones induced cell proliferation (cell counts), survival (Annexin-PI), viability (WST-1) and significantly reduced the expression of genes that inhibit cell cycle (p21, p16), promote mitochondrial apoptosis (Nix, PUMA) and tumor suppression (GDF-15, IGFBP-6), particularly in cells with high integrin expression. At last, we have confirmed that hypothyroid environment attenuated ovarian cancer growth using a novel experimental platform that exploited paired euthyroid and severe hypothyroid serum samples from human subjects. To conclude, our data define a critical role for thyroid hormones as potent αvβ3-ligands, driving ovarian cancer cell proliferation and suggest that disruption of this axis may present a novel treatment strategy in this aggressive disease.Oncogene advance online publication, 13 July 2015; doi:10.1038/onc.2015.262. © 2015 Macmillan Publishers Limited


Tsai C.-J.,Frederick National Laboratory for Cancer Research | Nussinov R.,Frederick National Laboratory for Cancer Research | Nussinov R.,Tel Aviv University
Seminars in Cancer Biology | Year: 2013

In this paper, we provide an overview of targeted anticancer therapies with small molecule kinase inhibitors. First, we discuss why a single constitutively active kinase emanating from a variety of aberrant genetic alterations is capable of transforming a normal cell, leading it to acquire the hallmarks of a cancer cell. To draw attention to the fact that kinase inhibition in targeted cancer therapeutics differs from conventional cytotoxic chemotherapy, we exploit a conceptual framework explaining why suppressed kinase activity will selectively kill only the so-called oncogene 'addicted' cancer cell, while sparing the healthy cell. Second, we introduce the protein kinase superfamily in light of its common active conformation with precisely positioned structural elements, and the diversified auto-inhibitory conformations among the kinase families. Understanding the detailed activation mechanism of individual kinases is essential to relate the observed oncogenic alterations to the elevated constitutively active state, to identify the mechanism of consequent drug resistance, and to guide the development of the next-generation inhibitors. To clarify the vital importance of structural guidelines in studies of oncogenesis, we explain how somatic mutations in EGFR result in kinase constitutive activation. Third, in addition to the common theme of secondary (acquired) mutations that prevent drug binding from blocking a signaling pathway which is hijacked by the aberrant activated kinase, we discuss scenarios of drug resistance and relapse by compensating lesions that bypass the inactivated pathway in a vertical or horizontal fashion. Collectively, these suggest that the future challenge of cancer therapy with small molecule kinase inhibitors will rely on the discovery of distinct combinations of optimized drugs to target individual subtypes of different cancers. © 2013 Elsevier Ltd.


Vaidman L.,Tel Aviv University
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2013

Misinterpretation in the preceding Comment of my recent analysis of the past of a photon is corrected. There is nothing in this analysis which is "contrary to the usual quantum expectations" but, nevertheless, it does provide "further understanding and interpretation of the system considered." In particular, it indicates that the common sense argument used in the Comment should be abandoned. © 2013 American Physical Society.


Ben-Horin S.,Tel Aviv University | Chowers Y.,Technion - Israel Institute of Technology
Nature Reviews Gastroenterology and Hepatology | Year: 2014

The treatment of IBD with anti-TNF agents has substantially evolved since their first introduction more than a decade ago. The robust efficacy witnessed in many patients has raised new questions pertaining to the observation of subgroups of patients who fail to respond or who lose response to these otherwise very effective drugs. Conversely, the exorbitant cost of biologic agents coupled with their efficacy in inducing lasting remission has introduced new concepts addressing the possibility of therapy cessation in some patients after deep remission has been achieved. Measuring drug and anti-drug antibody (ADA) levels which develop in some patients has emerged as a valuable tool in understanding the mechanisms responsible for some of these clinical scenarios. However, knowledge on how to use these measurements to guide clinical decisions in daily practice is still in its nascency and awaits prospective validation trials. Furthermore, as described in this Review, knowledgeable interpretation of drug and ADA test results mandates understanding the interplay between the technical profile of the assay used, the timing of the measurement in the drug cycle, assessment of disease activity, and the profoundly different pharmaco-clinical scenarios that can culminate in a similar test result. © 2014 Macmillan Publishers Limited.


Blum R.,New York University | Kloog Y.,Tel Aviv University
Cell Death and Disease | Year: 2014

Pancreatic ductal adenocarcinoma, an aggressively invasive, treatment-resistant malignancy and the fourth leading cause of cancer deaths in the United States, is usually detectable only when already inevitably fatal. Despite advances in genetic screening, mapping and molecular characterization, its pathology remains largely elusive. Renewed research interest in longstanding doctrines of tumor metabolism has led to the emergence of aberrant signaling pathways as critical factors modulating central metabolic networks that fuel pancreatic tumors. Such pathways, including those of Ras signaling, glutamine-regulatory enzymes, lipid metabolism and autophagy, are directly affected by genetic mutations and extreme tumor microenvironments that typify pancreatic tumor cells. Elucidation of these metabolic networks can be expected to yield more potent therapies against this deadly disease. © 2014 Macmillan Publishers Limited.


Vaidman L.,Tel Aviv University
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2013

Although there is no consensus regarding the "reality" of the past of a quantum particle, in situations where there is only one trajectory with a nonvanishing quantum wave of the particle between its emission and detection points, it seems "safe" to associate the past of the particle with this trajectory. A method for analyzing the past of a quantum particle according to the weak trace it leaves is proposed. Such a trace can be observed via measurements performed on an ensemble of identically pre- and postselected particles. Examples in which this method contradicts the above common sense description of the past of the particle are presented. It is argued that it is possible to describe the past of a quantum particle, but the naive approach has to be replaced by both forward- and backward-evolving quantum states. © 2013 American Physical Society.


Jablonka E.,Tel Aviv University
Progress in Biophysics and Molecular Biology | Year: 2013

Developmental plasticity, the capacity of a single genotype to give rise to different phenotypes, affects evolutionary dynamics by influencing the rate and direction of phenotypic change. It is based on regulatory changes in gene expression and gene products, which are partially controlled by epigenetic mechanisms. Plasticity involves not just epigenetic changes in somatic cells and tissues; it can also involve changes in germline cells. Germline epigenetic plasticity increases evolvability, the capacity to generate heritable, selectable, phenotypic variations, including variations that lead to novel functions. I discuss studies that show that some complex adaptive responses to new challenges are mediated by germline epigenetic processes, which can be transmitted over variable number of generations, and argue that the heritable variations that are generated epigenetically have an impact on both small-scale and large-scale aspects of evolution. First, I review some recent ecological studies and models that show that germline (gametic) epigenetic inheritance can lead to cumulative micro-evolutionary changes that are rapid and semi-directional. I suggest that " priming" and " epigenetic learning" may be of special importance in generating heritable, fine-tuned adaptive responses in populations. Second, I consider work showing how genomic and environmental stresses can also lead to epigenome repatterning, and produce changes that are saltational. © 2012 Elsevier Ltd.


Ringel Y.,University of North Carolina at Chapel Hill | Maharshak N.,University of North Carolina at Chapel Hill | Maharshak N.,Tel Aviv University
American Journal of Physiology - Gastrointestinal and Liver Physiology | Year: 2013

The pathophysiology of irritable bowel syndrome (IBS) is believed to involve alterations in the brain-gut axis; however, the etiological triggers and mechanisms by which these changes lead to symptoms of IBS remain poorly understood. Although IBS is often considered a condition without an identified "organic" etiology, emerging evidence suggests that alterations in the gastrointestinal microbiota and altered immune function may play a role in the pathogenesis of the disorder. These recent data suggest a plausible model in which changes in the intestinal microbiota and activation of the enteric immune system may impinge upon the brain-gut axis, causing the alterations in gastrointestinal function and the clinical symptoms observed in patients with IBS. This review summarizes the current evidence for altered intestinal microbiota and immune function in IBS. It discusses the potential etiological role of these factors, suggests an updated conceptual model for the pathogenesis of the disorder, and identifies areas for future research. © 2013 the American Physiological Society.


Bludov Y.V.,University of Minho | Konotop V.V.,University of Lisbon | Malomed B.A.,Tel Aviv University
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2013

We construct dark solitons in the recently introduced model of the nonlinear dual-core coupler with the mutually balanced gain and loss applied to the two cores, which is a realization of parity-time symmetry in nonlinear optics. The main issue is stability of the dark solitons. The modulational stability of the continuous-wave background, which supports the dark solitons, is studied analytically, and the full stability is investigated in a numerical form via computation of eigenvalues for modes of small perturbations. Stability regions are thus identified in the parameter space of the system and verified in direct simulations. Collisions between stable dark solitons are briefly considered too. © 2013 American Physical Society.


Roberts I.,Weatherall Institute of Molecular Medicine | Izraeli S.,Tel Aviv University
British Journal of Haematology | Year: 2014

Children with constitutional trisomy 21 (cT21, Down Syndrome, DS) are at a higher risk for both myeloid and B-lymphoid leukaemias. The myeloid leukaemias are often preceded by a transient neonatal pre-leukaemic syndrome, Transient Abnormal Myelopoiesis (TAM). TAM is caused by cooperation between cT21 and acquired somatic N-terminal truncating mutations in the key haematopoietic transcription factor GATA1. These mutations, which are not leukaemogenic in the absence of cT21, are found in almost one-third of neonates with DS. Analysis of primary human fetal liver haematopoietic cells and of human embryonic stem cells demonstrates that cT21 itself substantially alters human fetal haematopoietic development. Consequently, many haematopoietic developmental defects are observed in neonates with DS even in the absence of TAM. Although studies in mouse models have suggested a pathogenic role of deregulated expression of several chromosome 21-encoded genes, their role in human leukaemogenesis remains unclear. As cT21 exists in all embryonic cells, the molecular basis of cT21-associated leukaemias probably reflects a complex interaction between deregulated gene expression in haematopoietic cells and the fetal haematopoietic microenvironment in DS. © 2014 John Wiley & Sons Ltd.


Galperin M.,University of California at San Diego | Nitzan A.,University of California at San Diego | Nitzan A.,Tel Aviv University
Physical Chemistry Chemical Physics | Year: 2012

The interaction of light with molecular conduction junctions is attracting growing interest as a challenging experimental and theoretical problem on one hand, and because of its potential application as a characterization and control tool on the other. It stands at the interface between two important fields, molecular electronics and molecular plasmonics and has attracted attention as a challenging scientific problem with potentially important technological consequences. Here we review the present state of the art of this field, focusing on several key phenomena and applications: using light as a switching device, using light to control junction transport in the adiabatic and non-adiabatic regimes, light generation in biased junctions and Raman scattering from such systems. This field has seen remarkable progress in the past decade, and the growing availability of scanning tip configurations that can combine optical and electrical probes suggests that further progress towards the goal of realizing molecular optoelectronics on the nanoscale is imminent. © 2012 the Owner Societies.


Rokkas T.,Gastroenterology Clinic | Niv Y.,Tel Aviv University
European Journal of Gastroenterology and Hepatology | Year: 2012

Background: Video capsule endoscopy (VCE) is an attractive and patient friendly tool that provides high quality images of the small bowel. The reported yield of VCE in diagnosing celiac disease (CD) has shown variable results. Objective: The aim of this study was to assess the accuracy of VCE by pooling data of existing trials. DESIGN: Meta-analysis. The fixed-effects or random-effects model was used as appropriate, based on whether homogeneity or heterogeneity, respectively, was indicated by the Cochran Q-test. PATIENTS: Studies that estimated the accuracy of VCE were identified. The two investigators independently conducted the search and data extraction. A total of 166 individuals were included in this meta-analysis. Methods: An extensive literature search was performed and studies that estimated the accuracy of VCE in CD were identified. The two investigators independently conducted the search and data extraction. Data from the eligible studies were collected and pooled; sensitivity, specificity, likelihood ratios, and diagnostic odds ratios were computed. In addition, the results of the individual studies were displayed in a receiver operating characteristic (ROC) space to illustrate the distribution of sensitivities and specificities. A weighted symmetric summary ROC curve was computed and the area under the curve (AUC) was calculated, with perfect tests having an AUC of 1 and poor tests having an AUC close to 0.5. Results: Out of 461 titles initially generated by the literature searches, six studies met the inclusion criteria and were eligible for meta-analysis. The overall pooled VCE sensitivity was 89% [95% confidence interval (82-94%)] and specificity was 95% [95% confidence interval (89-98%)]. The AUC under the weighted symmetric summary ROC was 0.9584. Conclusion: The results of this meta-analysis mean that VCE, although it is not as accurate as pathology, could be a reasonable alternative method of diagnosing CD. Hopefully, this method will expand the portfolio of diagnostic methods available, especially in patients unwilling to undergo gastroscopy because of its perceived inconvenience and discomfort. However, larger, multicenter, and well-designed trials are needed to further establish the role of VCE in the diagnosis of CD. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Katzav E.,Kings College London | Schwartz M.,Tel Aviv University
IEEE Transactions on Signal Processing | Year: 2013

Superoscillating signals are band-limited signals that oscillate in some region faster their largest Fourier component. While such signals have many scientific and technological applications, their actual use is hampered by the fact that an overwhelming proportion of the energy goes into that part of the signal, which is not superoscillating. In the present paper, we consider the problem of optimization of such signals. The optimization that we describe here is that of the superoscillation yield, the ratio of the energy in the superoscillations to the total energy of the signal, given the range and frequency of the superoscillations. The constrained optimization leads to a generalized eigenvalue problem, which is solved numerically. It is noteworthy that it is possible to increase further the superoscillation yield at the cost of slightly deforming the oscillatory part of the signal, while keeping the average frequency. We show, how this can be done gradually, which enables a tradeoff between the distortion and the yield. We show how to apply this approach to nontrivial domains, and explain how to generalize this to higher dimensions. © 1991-2012 IEEE.


Yurovsky V.A.,Tel Aviv University | Olshanii M.,University of Massachusetts Boston
Physical Review Letters | Year: 2011

Two zero-range-interacting atoms in a circular, transversely harmonic waveguide are used as a test bench for a quantitative description of the crossover between integrability and chaos in a quantum system with no selection rules. For such systems we show that the expectation value after relaxation of a generic observable is given by a linear interpolation between its initial and thermal expectation values. The variable of this interpolation is universal; it governs this simple law to cover the whole spectrum of the chaotic behavior from integrable regime through the well-developed quantum chaos. The predictions are confirmed for the waveguide system, where the mode occupations and the trapping energy were used as the observables of interest; a variety of the initial states and a full range of the interaction strengths have been tested. © 2011 American Physical Society.


Gregory A.M.,University of London | Sadeh A.,Tel Aviv University
Sleep Medicine Reviews | Year: 2012

Links between sleep and psychopathology are complex and likely bidirectional. Sleep problems and alteration of normal sleep patterns have been identified in major forms of child psychopathology including anxiety, depression and attention disorders as well as symptoms of difficulties in the full range. This review summarizes some key findings with regard to the links between sleep and associated difficulties in childhood and adolescence. It then proposes a selection of possible mechanisms underlying some of these associations. Suggestions for future research include the need to 1) use multi-methods to assess sleep; 2) measure sleep in large-scale studies; 3) conduct controlled experiments to further establish the effects of sleep variations on emotional and behavioral difficulties; 4) take an interdisciplinary approach to further understand the links between sleep and associated difficulties. © 2011 Elsevier Ltd.


Lawn B.R.,U.S. National Institute of Standards and Technology | Lee J.J.-W.,U.S. National Institute of Standards and Technology | Chai H.,Tel Aviv University
Annual Review of Materials Research | Year: 2010

This paper addresses the durability of natural teeth from a materials perspective. Teeth are depicted as smart biocomposites, highly resistant to cumulative deformation and fracture. Favorable morphological features of teeth at both macroscopic and microscopic levels contribute to an innate damage tolerance. Damage modes are activated readily within the brittle enamel coat but are contained from spreading catastrophically into the vulnerable tooth interior in sustained occlusal loading. Although tooth enamel contains a multitude of microstructural defects that can act as sources of fracture, substantial overloads are required to drive any developing cracks to ultimate failure-nature's strategy is to contain damage rather than avoid it. Tests on model glass-shell systems simulating the basic elements of the tooth enamel/dentin layer structure help to identify important damage modes. Fracture and deformation mechanics provide a basis for analyzing critical conditions for each mode, in terms of characteristic tooth dimensions and materials properties. Comparative tests on extracted human and animal teeth confirm the validity of the model test approach and point to new research directions. Implications in biomechanics, especially as they relate to dentistry and anthropology, are outlined. © 2010 by Annual Reviews. All rights reserved.


Salasnich L.,University of Padua | Malomed B.A.,Tel Aviv University
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2013

We consider a binary Bose-Einstein condensate with linear and nonlinear interactions between its components, which emulate the spinor system with spin-orbit (SO) and Rabi couplings. For a relatively dense condensate, one-dimensional coupled equations with the nonpolynomial nonlinearity of both repulsive and attractive signs are derived from the three-dimensional Gross-Pitaevskii equations. Profiles of modes confined in an external potential under the action of the self-repulsion, and self-trapped solitons in the case of the self-attraction, are found in a numerical form and by means of analytical approximations. In the former case, the interplay of the SO and Rabi couplings with the repulsive nonlinearity strongly distorts shapes of the trapped modes, adding conspicuous sidelobes to them. In the case of the attractive nonlinearity, the most essential result is reduction of the collapse threshold under the action of the SO and Rabi couplings. © 2013 American Physical Society.


Zucker S.,Tel Aviv University
Monthly Notices of the Royal Astronomical Society: Letters | Year: 2016

We introduce an improvement to a periodicity metric we have introduced in a previous paper. We improve on the Hoeffding-test periodicity metric, using the Blum-Kiefer-Rosenblatt (BKR) test. Besides a consistent improvement over the Hoeffding-test approach, the BKR approach turns out to perform superbly when applied to very short time series of sawtooth-like shapes. The expected astronomical implications are much more detections of RR-Lyrae stars and Cepheids in sparse photometric data bases, and of eccentric Keplerian radial-velocity (RV) curves, such as those of exoplanets in RV surveys. © 2016 The Authors.


Kliper-Gross O.,Weizmann Institute of Science | Hassner T.,Open University of Israel | Wolf L.,Tel Aviv University
IEEE Transactions on Pattern Analysis and Machine Intelligence | Year: 2012

Recognizing actions in videos is rapidly becoming a topic of much research. To facilitate the development of methods for action recognition, several video collections, along with benchmark protocols, have previously been proposed. In this paper, we present a novel video database, the "Action Similarity LAbeliNg" (ASLAN) database, along with benchmark protocols. The ASLAN set includes thousands of videos collected from the web, in over 400 complex action classes. Our benchmark protocols focus on action similarity (same/not-same), rather than action classification, and testing is performed on never-before-seen actions. We propose this data set and benchmark as a means for gaining a more principled understanding of what makes actions different or similar, rather than learning the properties of particular action classes. We present baseline results on our benchmark, and compare them to human performance. To promote further study of action similarity techniques, we make the ASLAN database, benchmarks, and descriptor encodings publicly available to the research community. © 2012 IEEE.


Krivelevich M.,Tel Aviv University
Electronic Journal of Combinatorics | Year: 2012

We prove that if G is an (n, d, λ)-graph (a d-regular graph on n vertices, all of whose non-trivial eigenvalues are at most λ) and the following conditions are satisfied: for some constant ∈ > 0; 2. log d · log, then the number of Hamilton cycles in G is.


Geiger T.,Tel Aviv University | Zaidel-Bar R.,National University of Singapore
Current Opinion in Cell Biology | Year: 2012

Cell biologists studying cell adhesion have already figured out that cell-extracellular matrix connections, mediated by integrin receptors, are diverse and extremely complex structures. Dozens of adaptors-linking integrins with the cytoskeleton, and numerous enzymes and signaling proteins-regulating adhesion site dynamics, collectively referred to as the integrin adhesome, cooperate in mediating adhesion and activating specific signaling networks. Recent proteomic studies indicate that the known adhesome complexity is just the tip of the iceberg. In each existing category of molecular function the number of candidate components more than double the known components and several new categories are suggested. Proteomic analysis of different integrin heterodimers points to integrin-specific variations in composition and analysis of adhesion complexes under varying tension regimes highlights the force-dependent recruitment of different components, most notably LIM domain proteins. © 2012 Elsevier Ltd.


Nussinov R.,SAIC | Nussinov R.,Tel Aviv University | Tsai C.-J.,SAIC | Xin F.,Indiana University | Radivojac P.,Indiana University
Trends in Biochemical Sciences | Year: 2012

Post-translational modifications (PTMs) have been recognized to impact protein function in two ways: (i) orthosterically, via direct recognition by protein domains or through interference with binding; and (ii) allosterically, via conformational changes induced at the functional sites. Because different chemical types of PTMs elicit different structural alterations, the effects of combinatorial codes of PTMs are vastly larger than previously believed. Combined with orthosteric PTMs, the impact of PTMs on cellular regulation is immense. From an evolutionary standpoint, harnessing this immense, yet highly specific, PTM code is an extremely efficient vehicle that can save a cell several-fold in gene number and speed up its response to environmental change. © 2012 Elsevier Ltd.


Beck A.,Technion - Israel Institute of Technology | Teboulle M.,Tel Aviv University
SIAM Journal on Optimization | Year: 2012

We propose a unifying framework that combines smoothing approximation with fast first order algorithms for solving nonsmooth convex minimization problems. We prove that independently of the structure of the convex nonsmooth function involved, and of the given fast first order iterative scheme, it is always possible to improve the complexity rate and reach an O(ε -1) efficiency estimate by solving an adequately smoothed approximation counterpart. Our approach relies on the combination of the notion of smoothable functions that we introduce with a natural extension of the Moreau-infimal convolution technique along with its connection to the smoothing mechanism via asymptotic functions. This allows for clarification and unification of several issues on the design, analysis, and potential applications of smoothing methods when combined with fast first order algorithms. © 2012 Society for Industrial and Applied Mathematics.


Roditty L.,Bar - Ilan University | Zwick U.,Tel Aviv University
SIAM Journal on Computing | Year: 2012

We obtain three new dynamic algorithms for the approximate all-pairs shortest paths problem in unweighted undirected graphs: (i) For any fixed e > 0, a decremental algorithm with an expected total running time of Õ(mn), where m is the number of edges and n is the number of vertices in the initial graph. Each distance query is answered in O(1) worst-case time, and the stretch of the returned distances is at most 1+e. The algorithm uses Õ(n2) space. (ii) For any fixed integer k = 1, a decremental algorithm with an expected total running time of Õ (mn). Each query is answered in O(1) worst-case time, and the stretch of the returned distances is at most 2k - 1. This algorithm, however, uses only O(m + n1+1/k) space. It is obtained by dynamizing techniques of Thorup and Zwick. In addition to being more space efficient, this algorithm is also one of the building blocks used to obtain the first algorithm. (iii) For any fixed e, d > 0 and every t = m1/2-d, a fully dynamic algorithm with an expected amortized update time of Õ(mn/t) and worst-case query time of O(t). The stretch of the returned distances is at most 1+e. All algorithms can also be made to work on undirected graphs with small integer edge weights. If the largest edge weight is b, then all bounds on the running times are multiplied by b. © 2012 Society for Industrial and Applied Mathematics.


Nussinov R.,SAIC | Nussinov R.,Tel Aviv University
Molecular BioSystems | Year: 2012

Communication is essential. It is vital between cells in multi-cellular organisms, and within cells. A signaling molecule binds to a receptor protein, and initiates a cascade of dynamic events. Signaling is a multistep pathway, which allows signal amplification: if some of the molecules in a pathway transmit the signal to multiple molecules, the result can be a large number of activated molecules across the cell and multiple reactions. That is how a small number of extracellular signaling molecules can produce a major cellular response. The pathway can relay signals from the extracellular space to the nucleus. How do signals travel efficiently over long-distances across the cell? Here we argue that evolution has utilized three properties: a modular functional organization of the cellular network; sequences in some key regions of proteins, such as linkers or loops, which were pre-encoded by evolution to facilitate signaling among domains; and compact interactions between proteins which is achieved via conformational disorder.


The 1990s saw two different and even contradictory trends in Israel. On the one hand, there was a substantial increase in environmental awareness, on the part of both the general public and decision-makers, that led to a change in the land use planning policy at the national level. On the other hand, the Israel Lands Council (ILC), the body empowered by law to shape the national land policy, made a series of decisions that severely violated the principle of preserving agricultural land and led to massive conversion of agricultural land and open space for commercial, industrial, and residential development. Thus the national land policy became incompatible with the land use planning policy and the rise in environmental awareness it reflected.The purpose of this paper is to examine the changes in the ILC members' attitudes toward the principle of preserving agricultural land. The findings point to a complex and ambivalent relationship, in Israel's national land policy, between Zionist-nationalist considerations and the principle of preserving agricultural land. They also point to fundamental changes in this relationship over time. The analysis that follows can explain the incompatibility between the land use planning policy and the national land policy. © 2010 Elsevier Ltd.


Banks-Sills L.,Tel Aviv University
Applied Mechanics Reviews | Year: 2010

Since the previous paper was written (Banks-Sills, 1991, "Application of the Finite Element Method to Linear Elastic Fracture Mechanics," Appl. Mech. Rev., 44, pp. 447-461), much progress has been made in applying the finite element method to linear elastic fracture mechanics. In this paper, the problem of calculating stress intensity factors in two- and three-dimensional mixed mode problems will be considered for isotropic and anisotropic materials. The square-root singular stresses in the neighborhood of the crack tip will be modeled by quarter-point, square and collapsed, triangular elements for twodimensional problems, respectively, and by brick and collapsed, prismatic elements in three dimensions. The stress intensity factors are obtained by means of the interaction energy or M-integral. Displacement extrapolation is employed as a check on the results. In addition, the problem of interface cracks between homogeneous, isotropic, and anisotropic materials is presented. The purpose of this paper is to present an accurate and efficient method for calculating stress intensity factors for mixed mode deformation. The equations presented here should aid workers in this field to carry out similar analyses, as well as to check their calculations with respect to the examples described. © 2010 by ASME.


Pick E.,Tel Aviv University
Methods in Molecular Biology | Year: 2014

The superoxide (O2 •- )-generating NADPH oxidase complex of phagocytes comprises a membraneimbedded heterodimeric fl avocytochrome, known as cytochrome b558 (consisting of Nox2 and p22phox ) and four cytosolic regulatory proteins, p47phox , p67phox , p40phox , and the small GTPase Rac. Under physiological conditions, in the resting phagocyte, O2 •- generation is initiated by engagement of membrane receptors by a variety of stimuli, followed by specifi c signal transduction sequences leading to the translocation of the cytosolic components to the membrane and their association with the cytochrome. A consequent conformational change in Nox2 initiates the electron "fl ow" along a redox gradient, from NADPH to oxygen, leading to the one-electron reduction of molecular oxygen to O 2 •- . Methodological diffi culties in the dissection of this complex mechanism led to the design "cell-free" systems (also known as "broken cells" or in vitro systems). In these, membrane receptor stimulation and all or part of the signal transduction sequence are missing, the accent being placed on the actual process of "NADPH oxidase assembly," thus on the formation of the complex between cytochrome b 558 and the cytosolic components and the resulting O2 •- generation. Cell-free assays consist of a mixture of the individual components of the NADPH oxidase complex, derived from resting phagocytes or in the form of purifi ed recombinant proteins, exposed in vitro to an activating agent (distinct from and unrelated to whole cell stimulants), in the presence of NADPH and oxygen. Activation is commonly quantifi ed by measuring the primary product of the reaction, O2 •- , trapped immediately after its generation by an appropriate acceptor in a kinetic assay, permitting the calculation of the linear rate of O 2 •- production, but numerous variations exist, based on the assessment of reaction products or the consumption of substrates. Cell-free assays played a paramount role in the identifi cation and characterization of the components of the NADPH oxidase complex, the deciphering of the mechanisms of assembly, the search for inhibitory drugs, and the diagnosis of various forms of chronic granulomatous disease (CGD). © 2014 Springer Science+Business Media, LLC.


Palamodov V.P.,Tel Aviv University
Inverse Problems | Year: 2012

A new method for analytic inversion of Radon-type integral transforms is proposed. © 2012 IOP Publishing Ltd.


Comparison of the growth velocity of 1 vs. 2 IGF-I injections per day in patients with Laron Syndrome (primary GH insensitivity) revealed similar effects.


The cerebellum is commonly studied in the context of the classical eyeblink conditioning model, which attributes an adaptive motor function to cerebellar learning processes. This model of cerebellar function has quite a few shortcomings and may in fact be somewhat deficient in explaining the myriad functions attributed to the cerebellum, functions ranging from motor sequencing to emotion and cognition. The involvement of the cerebellum in these motor and non-motor functions has been demonstrated in both animals and humans in electrophysiological, behavioral, tracing, functional neuroimaging, and PET studies, as well as in clinical human case studies. A closer look at the cerebellum's evolutionary origin provides a clue to its underlying purpose as a tool which evolved to aid predation rather than as a tool for protection. Based upon this evidence, an alternative model of cerebellar function is proposed, one which might more comprehensively account both for the cerebellum's involvement in a myriad of motor, affective, and cognitive functions and for the relative simplicity and ubiquitous repetitiveness of its circuitry. This alternative model suggests that the cerebellum has the ability to detect coincidences of events, be they sensory, motor, affective, or cognitive in nature, and, after having learned to associate these, it can then trigger (or "mirror") these events after having temporally adjusted their onset based on positive/negative reinforcement. The model also provides for the cerebellum's direction of the proper and uninterrupted sequence of events resulting from this learning through the inhibition of efferent structures (as demonstrated in our lab). © Springer Science+Business Media New York 2013.


Keating B.G.,University of California at San Diego | Shimon M.,Tel Aviv University | Yadav A.P.S.,University of California at San Diego
Astrophysical Journal Letters | Year: 2013

Precision measurements of the polarization of the cosmic microwave background (CMB) radiation, especially experiments seeking to detect the odd-parity "B-modes," have far-reaching implications for cosmology. To detect the B-modes generated during inflation, the flux response and polarization angle of these experiments must be calibrated to exquisite precision. While suitable flux calibration sources abound, polarization angle calibrators are deficient in many respects. Man-made polarized sources are often not located in the antenna's far-field, have spectral properties that are radically different from the CMB's, are cumbersome to implement, and may be inherently unstable over the (long) duration these searches require to detect the faint signature of the inflationary epoch. Astrophysical sources suffer from time, frequency, and spatial variability, are not visible from all CMB observatories, and none are understood with sufficient accuracy to calibrate future CMB polarimeters seeking to probe inflationary energy scales of 10 15 GeV. Both man-made and astrophysical sources require dedicated observations which detract from the amount of integration time usable for detection of the inflationary B-modes. CMB TB and EB modes, expected to identically vanish in the standard cosmological model, can be used to calibrate CMB polarimeters. By enforcing the observed EB and TB power spectra to be consistent with zero, CMB polarimeters can be calibrated to levels not possible with man-made or astrophysical sources. All of this can be accomplished for any polarimeter without any loss of observing time using a calibration source which is spectrally identical to the CMB B-modes. © 2013. The American Astronomical Society. All rights reserved..


Peer D.,Laboratory of NanoMedicine | Peer D.,Tel Aviv University
Immunological Reviews | Year: 2013

RNA interference (RNAi) has advanced into clinical trials. In spite of the progress made in systemic RNAi delivery to the liver and solid tumors, delivery of RNAi to leukocytes remains challenging and less advanced. Manipulating leukocyte function with RNAi holds great promise for streamlining the drug discovery process by facilitating in vivo drug target validation and for facilitating the development of RNAi-based therapy platforms for leukocyte-implicated diseases, such as blood cancer, inflammation, and leukocyte-tropic viral infections. In this review, progress in delivery strategies of RNAi payloads to leukocytes, which are notoriously difficult cells to transduce with RNAi, is discussed with special emphasis on the challenges and potential opportunities for manipulating leukocyte function with RNAi. © 2013 John Wiley & Sons A/S.


Chai H.,Tel Aviv University
International Journal of Solids and Structures | Year: 2011

Studies on channel cracking are generally limited to elastic films on elastic or inelastic substrates. There are important applications were the cracking process involves extensive plasticity in both the film and substrate, however. In this work steady-state channel cracking in inelastic thin-film bilayers undergoing large-scale yielding from thermal or mechanical loading is studied with the aid of a plane-strain FEA. The plasticity of the film and substrate, represented by a Ramberg-Osgood constitutive law, each increases the energy release rate (ERR) relative to the linearly-elastic case. This effect is more pronounced under mechanical loading where the entire bilayer undergoes large-scale yielding. To help assess the analytic approach some fragmentation tests are performed using a well-bonding epoxy/aluminum system. The analysis reproduced well the observed dependence of crack initiation strain on film thickness. Ultra-thin films may be well represented by an elastic-perfectly plastic response. For such films on a flexible support the ERR remains fixed as the applied strain exceeds the yield strain of the film. Accordingly, a critical coating thickness exists below which no channel cracking is possible. The explicit relations and graphical data presented may be used for optimal design of such structures against premature failure as well as for determining fracture energy of ductile thin films. © 2011 Elsevier Ltd. All rights reserved.


Rozen S.,Tel Aviv University
Advanced Synthesis and Catalysis | Year: 2010

Although known for more than a century, bromine trifluoride is not a common reagent in day to day research work in organic chemistry. Its tendency to react exothermically with solvents containing Lewis base elements such as water, acetone or ethers distanced it from the mind of many. Still, under the proper conditions, it can perform quite a few selective reactions which are difficult to achieve by other reagents. We discuss in this review reactions which have been published in the last 30 years. They consist of fluorinating heteroatoms, substituting carbon-halogen bonds with carbon-fluorine bonds, syntheses of anesthetics, construction of the trifluoromethyl (CF3) and the difluoromethylene (CF2) groups, aromatic brominations and more. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Helled R.,Tel Aviv University | Guillot T.,University of Nice Sophia Antipolis
Astrophysical Journal | Year: 2013

The accurate determination of Saturn's gravitational coefficients by Cassini could provide tighter constraints on Saturn's internal structure. Also, occultation measurements provide important information on the planetary shape which is often not considered in structure models. In this paper we explore how wind velocities and internal rotation affect the planetary shape and the constraints on Saturn's interior. We show that within the geodetic approach the derived physical shape is insensitive to the assumed deep rotation. Saturn's re-derived equatorial and polar radii at 100 mbar are found to be 54,445 ± 10 km and 60,365 ± 10 km, respectively. To determine Saturn's interior, we use one-dimensional three-layer hydrostatic structure models and present two approaches to include the constraints on the shape. These approaches, however, result in only small differences in Saturn's derived composition. The uncertainty in Saturn's rotation period is more significant: with Voyager's 10h39m period, the derived mass of heavy elements in the envelope is 0-7 M ⊕. With a rotation period of 10 h32m, this value becomes <4 M ⊕, below the minimum mass inferred from spectroscopic measurements. Saturn's core mass is found to depend strongly on the pressure at which helium phase separation occurs, and is estimated to be 5-20 M ⊕. Lower core masses are possible if the separation occurs deeper than 4 Mbar. We suggest that the analysis of Cassini's radio occultation measurements is crucial to test shape models and could lead to constraints on Saturn's rotation profile and departures from hydrostatic equilibrium. © 2013. The American Astronomical Society. All rights reserved..


Shechter M.,Tel Aviv University
Magnesium Research | Year: 2010

Hypomagnesemia is common in hospitalized patients, especially in the elderly with coronary artery disease (CAD) and/or those with chronic heart failure. Hypomagnesemia is associated with an increased incidence of diabetes mellitus, metabolic syndrome, mortality rate from CAD and all causes. Magnesium supplementation improves myocardial metabolism, inhibits calcium accumulation and myocardial cell death; it improves vascular tone, peripheral vascular resistance, afterload and cardiac output, reduces cardiac arrhythmias and improves lipid metabolism. Magnesium also reduces vulnerability to oxygen-derived free radicals, improves human endothelial function and inhibits platelet function, including platelet aggregation and adhesion, which potentially gives magnesium physiologic and natural effects similar to adenosine-diphosphate inhibitors such as clopidogrel. The data regarding its use in patients with acute myocardial infarction (AMI) is conflicting. Although some previous, relatively small randomized clinical trials demonstrated a remarkable reduction in mortality when administered to relatively high risk AMI patients, two recently published large-scale randomized clinical trials (the Fourth International Study of Infarct Survival and Magnesium in Coronaries) failed to show any advantage of intravenous magnesium over placebo. Nevertheless, there are theoretical potential benefits of magnesium supplementation as a cardioprotective agent in CAD patients, as well as promising results from previous work in animal and humans. These studies are cost effective, easy to handle and are relatively free of adverse effects, which gives magnesium a role in treating CAD patients, especially high-risk groups such as CAD patients with heart failure, the elderly and hospitalized patients with hypomagnesemia. Furthermore, magnesium therapy is indicated in life-threatening ventricular arrhythmias such as Torsades de Pointes and intractable ventricular tachycardia.


Alsop G.I.,University of Aberdeen | Marco S.,Tel Aviv University
Tectonophysics | Year: 2013

The Late Pleistocene Lisan Formation contains superb examples of soft-sediment deformation generated during gravity-driven slumping and failure down extremely gentle (<. 1°) slopes towards the palaeo-Dead Sea Basin. Following a previously established framework, portions of individual slumps are broadly categorised into coherent, semi-coherent, and incoherent domains, reflecting increasing deformation and disarticulation of sediment. We present new structural data collected from each of these (overlapping) domains that demonstrate how the orientation of fold hinges and axial planes becomes more dispersed as slumps become increasingly incoherent. Such patterns are the reverse to that typically encountered in lithified rocks where increasing deformation results in clustering of linear elements towards the flow direction, and may reflect greater heterogeneity and disarticulation within slumps. Use of folds to determine palaeoslopes should therefore be limited to those from coherent slumps, where the opportunity for hinge dislocation and rotation is more limited. Within coherent and semi-coherent slumps, folds are reworked to create classic Type 1, 2 and 3 refold patterns during a single progressive deformation perhaps lasting just a matter of minutes. It is noteworthy that slump folds are typically lacking in smaller parasitic folds, implying that instantaneous development and/or limited viscosity contrasts have hindered the formation of second order folds. As deformation intensifies within semi-coherent to incoherent slumps, some fold hinges rotate towards the flow direction to create sheath folds. However, many fold hinges do not rotate into the flow direction, but rather roll downslope to form a new category of spiral folds. Extreme deformation may also generate semi-detached fold trains in which the short limbs of verging fold pairs are relatively thickened resulting in en-echelon X folds. The hinges of the sheared fold pair are reduced to apophyses, although these can still be used to infer original fold vergence. As observations are from a thin slumped system over a relatively small area, the variation in structural style from coherent to incoherent is attributed to increasing deformation.© 2013 Elsevier B.V.


Cremonesi S.,Tel Aviv University
Journal of High Energy Physics | Year: 2011

We study type IIB brane configurations engineering 3d flavoured ABJ(M) theories with Yang-Mills kinetic terms, which flow to IR fixed points describing M2 branes at a class of toric Calabi-Yau fourfold singularities. The type IIB construction provides a bridge between M-theory geometry and field theory, and allows to identify the superconformal field theories with fixed quiver diagram, Chern-Simons levels and superpotential, differing by the ranks of the gauge groups, which we associate to dual AdS4 × Y7 backgrounds of M-theory without or with torsion G-fluxes sourced by fractional M2 branes in Y7, when Y7 is smooth. The analysis includes the Q1,1,1 and Y1,2(CP2) geometries. We also comment on duality cascades and on the interplay between torsion G-fluxes in M-theory and partial resolutions. © SISSA 2011.


Wool A.,Tel Aviv University
IEEE Internet Computing | Year: 2010

The first quantitative evaluation of the quality of corporate firewall configurations appeared in 2004, based on Check Point Firewall-1 rule sets. In general, that survey indicated that corporate firewalls often enforced poorly written rule sets. This article revisits the first survey. In addition to being larger, the current study includes configurations from two major vendors. It also introduces a firewall complexity. The study's findings validate the 2004 study's main observations: firewalls are (still) poorly configured, and a rule-set's complexity is (still) positively correlated with the number of detected configuration errors. However, unlike the 2004 study, the current study doesn't suggest that later software versions have fewer errors. © 2006 IEEE.


Levinson A.,Tel Aviv University
Astrophysical Journal | Year: 2010

The interaction of relativistic magnetized ejecta with an ambient medium is studied for a range of structures and magnetization of the unshocked ejecta. We particularly focus on the effect of the ambient medium on the dynamics of an impulsive, high-sigma shell. It is found that for sufficiently high values of the initial magnetization σ0 the evolution of the system is significantly altered by the ambient medium well before the shell reaches its coasting phase. The maximum Lorentz factor of the shell is limited to values well below σ0; for a shell of initial energy E = 10 52 E52 erg and size r0 = 1012 T 30 cm expelled into a medium having a uniform density ni, we obtain Γmax ≃ 180(E52/T30 3ni)1/8 in the high-sigma limit. The reverse shock and any internal shocks that might form if the source is fluctuating are shown to be very weak. The restriction on the Lorentz factor is more severe for shells propagating in a stellar wind. Intermittent ejection of small sub-shells does not seem to help, as the shells merge while still highly magnetized. Lower sigma shells start decelerating after reaching the coasting phase and spreading away. The properties of the reverse shock then depend on the density profiles of the coasting shell and the ambient medium. For a self-similar cold shell the reverse shock becomes strong as it propagates inward, and the system eventually approaches the self-similar solution recently derived by Nakamura & Shigeyama. © 2010. The American Astronomical Society. All rights reserved. Printed in the U.S.A.


Izraeli S.,Tel Aviv University
British Journal of Haematology | Year: 2010

The remarkable progress in the treatment of childhood acute lymphoblastic leukaemia (ALL) has been based on the adjustment of therapy to subgroups of leukaemia stratified by their prognostic implications. Here, the contribution of the last decade of advanced genomic research on the clinical management of childhood ALL is examined. The application of genomics for routine diagnosis of ALL is feasible but depends on commercial development of appropriate certified platforms. The discovery of several novel high-risk markers, such as deletions in IKZF1 might be integrated into clinical protocols in the near future. Several novel targets for therapy have been identified and have led to phase I/II therapeutic trials. This and any future progress depends on the maintenance of high quality bio-banks including biological material and clinical data of each patient enrolled on a prospective clinical protocol. © 2010 Blackwell Publishing Ltd.


Carmon D.,Tel Aviv University
Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences | Year: 2015

We prove a function field version of Chowla's conjecture on the autocorrelation of the Möbius function in the limit of a large finite field of characteristic 2, extending previous work in odd characteristic. © 2015 The Author(s) Published by the Royal Society. All rights reserved.


Rabinovich A.,Tel Aviv University
International Journal of Thermal Sciences | Year: 2015

We solve the problem of heat conduction in a 2D homogeneous medium (of diffusivity ±) below a boundary subjected to time-periodic temperature (of frequency ‰), in the presence of a circular inhomogeneity (of radius R), whose center is at distance d > R (depth) from the boundary. This study is a continuation of a previous one which considers a 3D medium with a spherical inhomogeneity. The general solution depends on four dimensionless parameters: d/R, the heat conductivity ratio °, the heat capacity ratio C and the displacement thickness RCombining double low line2±/‰R2). An analytical solution is derived as an infinite series of eigenfunctions pertaining to the 2D Helmholtz equation. The solution converges quickly and is shown to be in agreement with a finite element numerical solution. The results are illustrated and analyzed for a given accuracy and for a few values of the governing parameters. A comparison is held with the previous 3D solution pointing out the differences between the two. To widen the range of possible applications, an extension of the solution to a domain of finite depth is also presented. The general solution can be simplified considerably for asymptotic values of the parameters. A first approximation, obtained for R/d‰1, pertains to an unbounded domain. A further approximate solution, for R/d‰1, while ° and C are fixed, can be regarded as pertaining to a quasi-steady regime. However, its accuracy deteriorates for R/d ‰ 1, and a solution, coined as the insulated circle approximation, is derived for this case. Comparison with the exact solution shows that these approximations are accurate for a wide range of parameter values. © 2014 Elsevier Masson SAS.


Maoz D.,Tel Aviv University | Sharon K.,University of Chicago | Gal-Yam A.,Weizmann Institute of Science
Astrophysical Journal | Year: 2010

Knowledge of the supernova (SN) delay time distribution (DTD)-the SN rate versus time that would follow a hypothetical brief burst of star formation-can shed light on SN progenitors and physics, as well as on the timescales of chemical enrichment in different environments. We compile recent measurements of the Type-Ia SN (SN Ia) rate in galaxy clusters at redshifts from z = 0 out to z = 1.45, just 2 Gyr after cluster star formation at z ≈ 3. We review the plausible range for the observed total iron-to-stellar mass ratio in clusters, based on the latest data and analyses, and use it to constrain the time-integrated number of SN Ia events in clusters. With these data, we recover the DTD of SNe Ia in cluster environments. The DTD is sharply peaked at the shortest time-delay interval we probe, 0 Gyr < t < 2.2 Gyr, with a low tail out to delays of ∼10 Gyr, and is remarkably consistent with several recent DTD reconstructions based on different methods, applied to different environments. We test DTD models from the literature, requiring that they simultaneously reproduce the observed cluster SN rates and the observed iron-to-stellar mass ratios. A parameterized power-law DTD of the form t -1.2±03 from t = 400 Myr to a Hubble time can satisfy both constraints. Shallower power laws such as t-1/2 cannot, assuming a single DTD, and a single star formation burst (either brief or extended) at high z. This implies that 50%-85% of SNe Ia explode within 1 Gyr of star formation. DTDs from double-degenerate (DD) models, which generically have ∼t -1 shapes over a wide range of timescales, match the data, but only if their predictions are scaled up by factors of 5-10. Single-degenerate (SD) DTDs always give poor fits to the data, due to a lack of delayed SNe and overall low numbers of SNe. The observations can also be reproduced with a combination of two SN Ia populations-a prompt SD population of SNe Ia that explodes within a few Gyr of star formation, and produces about 60% of the iron mass in clusters, and a DD population that contributes the events seen at z < 1.5. An alternative scenario of a single, prompt, SN Ia population, but a composite star formation history in clusters, consisting of a burst at high z, followed by a constant star formation rate, can reproduce the SN rates, but is at odds with direct measurements of star formation in clusters at 0 < z < 1. Our results support the existence of a DD progenitor channel for SNe Ia, if the overall predicted numbers can be suitably increased. © 2010. The American Astronomical Society. All rights reserved. Printed in the U.S.A.


Vaidman L.,Tel Aviv University
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2014

The question "Where was a quantum particle between pre- and postselection measurements?" is analyzed in view of a recent proposal that the quantum particle was in the overlap of the forward and backward evolving wave functions. It is argued that this proposal corresponds not only to the criterion of where the particle leaves a weak trace but also to the criterion of where the local interactions can affect the probability of postselection and where finding the particle in a strong nondemolition measurement is possible. The concept of a "secondary presence" of a pre- and postselected particle where local interactions affect the weak trace in the overlap region is introduced. © 2014 American Physical Society.


Breiman A.,Tel Aviv University
Current Protein and Peptide Science | Year: 2014

Molecular chaperones, central to cellular protein homeostasis, are conserved within species. Hsp90 and its cochaperones participate in major cellular functions such as cell growth, response to biotic and abiotic stresses and differentiation, and are critical to the regulation of these functions. Regulation is done through their interacting with client proteins in various cellular compartments under specific conditions. Plant Hsp90 and its co-chaperones resemble their mammalian counterparts in their structure. They were shown to participate in diverse and unique pathways such as defense mechanism against pathogens, regulation of gene expression by regulation of the silencing of RNAs, transport of pre-proteins into chloroplasts and response to heat stress. In many cases, the Hsp90 interaction with the co-chaperone is a prerequisite to interaction with client proteins and regulation of their function. While our understanding of the interaction of plant Hsp90 and its co-chaperones has been greatly enhanced, the large number of isoforms in plants and the diverse molecular pathways specific to plants still leave many open questions about the regulation, specificity, and biophysical characteristics of the complexes formed and their contribution to the cellular homeostasis. © 2014 Bentham Science Publishers.


Dinstein Y.,Tel Aviv University
Journal of Conflict and Security Law | Year: 2012

Computer Network Attacks (CNAs) do not automatically come within the framework of the definition of 'attack' in conformity with the law of armed conflict (LOAC). Consequently, some so-called CNAs (especially, those used only as means of intelligence gathering) do not qualify as 'attacks' in the sense of LOAC. Only CNAs entailing 'violence' do. CNAs constituting 'attacks' in the LOAC sense are governed by the same rules that apply to kinetic attacks. In particular, they are subject to the application of the cardinal principle of distinction between combatants/military objectives and civilians/civilian objects. Consequently, deliberate attacks against civilians/civilian objects are prohibited, and so are indiscriminate attacks. An important extrapolation of the principle of distinction is the principle of proportionality, whereby-when lawful targets are attacked-collateral damage to civilians/civilian objects must not be expected to be 'excessive' compared with the military advantage anticipated. This is a complex construct, applying to CNAs as much as to other attacks. Feasible precautions must be taken prior to any attack, including a CNA. When a civilian is engaged in any form in a CNA, the act constitutes direct participation in hostilities and the actor loses civilian protection from attack. © Oxford University Press 2012; all rights reserved.


Katz D.,Tel Aviv University
Global Environmental Politics | Year: 2011

Predictions of inevitable and imminent wars over scarce water are routinely made by prominent political figures, academics, journalists, and non-governmental organizations (NGOs). These statements continue to occur despite both a questionable theoretical foundation and little empirical evidence to support them. This study demonstrates that several sets of actors-policymakers, academics, journalists, and NGO activists each have different incentives to stress and even exaggerate the probability of war over water. This confluence of incentives has likely contributed to an overemphasis in public discourse of the likelihood of water wars. © 2011 by the Massachusetts Institute of Technology.


Bazak L.,Bar - Ilan University | Levanon E.Y.,Bar - Ilan University | Eisenberg E.,Tel Aviv University
Nucleic Acids Research | Year: 2014

A-to-I RNA editing is apparently the most abundant post-transcriptional modification in primates. Virtually all editing sites reside within the repetitive Alu SINEs. Alu sequences are the dominant repeats in the human genome and thus are likely to pair with neighboring reversely oriented repeats and form double-stranded RNA structures that are bound by ADAR enzymes. Editing levels vary considerably between different adenosine sites within Alu repeats. Part of the variability has been explained by local sequence and structural motifs. Here, we focus on global characteristics that affect the editability at the Alu level. We use large RNA-seq data sets to analyze the editing levels in 203 798 Alu repeats residing within human genes. The most important factor affecting Alu editability is its distance to the closest reversely oriented neighbor-average editability decays exponentially with this distance, with a typical distance of ∼800 bp. This effect alone accounts for 28% of the total variance in editability. In addition, the number of Alu repeats of the same and reverse strand in the genomic vicinity, the expressed strand of the Alu, Alu's length and subfamily and the occurrence of reversely oriented neighbor in the same intron\exon all contribute, to a lesser extent, to the Alu editability. © 2014 The Author(s) 2014.


Signaling by bone morphogenetic protein (BMP) receptors is regulated at multiple levels in order to ensure proper interpretation of BMP stimuli in different cellular settings. As with other signaling receptors, regulation of the amount of exposed and signaling-competent BMP receptors at the plasma-membrane is predicted to be a key mechanism in governing their signaling output. Currently, the endocytosis of BMP receptors is thought to resemble that of the structurally related transforming growth factor-β (TGF-β) receptors, as BMP receptors are constitutively internalized (independently of ligand binding), with moderate kinetics, and mostly via clathrin-mediated endocytosis. Also similar to TGF-β receptors, BMP receptors are able to signal from the plasma membrane, while internalization to endosomes may have a signal modulating effect. When at the plasma membrane, BMP receptors localize to different membrane domains including cholesterol rich domains and caveolae, suggesting a complex interplay between membrane distribution and internalization. An additional layer of complexity stems from the putative regulatory influence on the signaling and trafficking of BMP receptors exerted by ligand traps and/or co-receptors. Furthermore, the trafficking and signaling of BMP receptors are subject to alterations in cellular context. For example, genetic diseases involving changes in the expression of auxiliary factors of endocytic pathways hamper retrograde BMP signals in neurons, and perturb the regulation of synapse formation. This review summarizes current understanding of the trafficking of BMP receptors and discusses the role of trafficking in regulation of BMP signals. © 2015 Elsevier Ltd.


Schuss Z.,Tel Aviv University
Journal of Physical Chemistry C | Year: 2010

We examine the assumptions and conclusion of (generalized) transition state theory (GTST) by considering the activation process in the diffusion (Langevin) limit. We find the asymptotic structure of the leading eigenfunctions and eigenvalues of the Fokker-Planck operator with a bistable potential and hence the longtime quasi-equilibrium behavior of the phase space probability density function (pdf). Defining reactant and product as small neighborhoods of the stable states, we examine all possible recrossings of the transition state region (TSR) and find their contribution to the mean first passage time (MFPT) from one state to the other. We show that the mean number of recrossings of the TSR is 1, so the MFPT from one state to the other is twice that to the stochastic separatrix, which we use as a generalized transition state (GTS). The activation rate, that is, the rate at which trajectories arrive from one state to the other, is then shown to be one-half of the arrival rate at the GTS and in the limit of a high barrier is independent of the choice of the size of the domains that define the states. We conclude that to obtain the correct rate in (G)TST (i) the quasi-equilibrium density (qepdf) rather than the equilibrium density (epdf) has to be used, (ii) the qepdf contains a boundary layer near the stochastic separatrix, but otherwise the reactant qepdf is nearly equal the epdf, and (iii) all recrossings of the (G)TS are accounted for if the (G)TS is the stochastic separatrix, but not otherwise. We also consider the case of a single metastable state. © 2010 American Chemical Society.


Chelouche D.,Haifa University | Zucker S.,Tel Aviv University
Astrophysical Journal | Year: 2013

A generalized approach to reverberation mapping (RM) is presented, which is applicable to broad- and narrowband photometric data, as well as to spectroscopic observations. It is based on multivariate correlation analysis techniques and, in its present implementation, is able to identify reverberating signals across the accretion disk and the broad-line region (BLR) of active galactic nuclei (AGNs). Statistical tests are defined to assess the significance of time-delay measurements using this approach, and the limitations of the adopted formalism are discussed. It is shown how additional constraints on some of the parameters of the problem may be incorporated into the analysis thereby leading to improved results. When applied to a sample of 14 Seyfert 1 galaxies having good-quality high-cadence photometric data, accretion disk scales and BLR sizes are simultaneously determined, on a case-by-case basis, in most objects. The BLR scales deduced here are in good agreement with the findings of independent spectroscopic RM campaigns. Implications for the photometric RM of AGN interiors in the era of large surveys are discussed. © 2013. The American Astronomical Society. All rights reserved.


Piro A.L.,California Institute of Technology | Nakar E.,Tel Aviv University
Astrophysical Journal | Year: 2013

The light curve of the explosion of a star with a radius ≲ 10-100 R⊙ is powered mostly by radioactive decay. Observationally, such events are dominated by hydrogen-deficient progenitors and classified as Type I supernovae (SNe I), i.e., white dwarf thermonuclear explosions (Type Ia), and core collapses of hydrogen-stripped massive stars (Type Ib/c). Current transient surveys are finding SNe I in increasing numbers and at earlier times, allowing their early emission to be studied in unprecedented detail. Motivated by these developments, we summarize the physics that produces their rising light curves and discuss ways in which observations can be utilized to study these exploding stars. The early radioactive-powered light curves probe the shallowest deposits of 56Ni. If the amount of 56Ni mixing in the outermost layers of the star can be deduced, then it places important constraints on the progenitor and properties of the explosive burning. In practice, we find that it is difficult to determine the level of mixing because it is hard to disentangle whether the explosion occurred recently and one is seeing radioactive heating near the surface or whether the explosion began in the past and the radioactive heating is deeper in the ejecta. In the latter case, there is a "dark phase" between the moment of explosion and the first observed light emitted once the shallowest layers of 56Ni are exposed. Because of this, simply extrapolating a light curve from radioactive heating back in time is not a reliable method for estimating the explosion time. The best solution is to directly identify the moment of explosion, either through observing shock breakout (in X-ray/UV) or the cooling of the shock-heated surface (in UV/optical), so that the depth being probed by the rising light curve is known. However, since this is typically not available, we identify and discuss a number of other diagnostics that are helpful for deciphering how recently an explosion occurred. As an example, we apply these arguments to the recent SN Ic PTF 10vgv. We demonstrate that just a single measurement of the photospheric velocity and temperature during the rise places interesting constraints on its explosion time, radius, and level of 56Ni mixing. © 2013. The American Astronomical Society. All rights reserved.


Mizrachi N.,Tel Aviv University
Culture, Medicine and Psychiatry | Year: 2014

This study examines how Muslim religious leaders (imams) introduce the liberal notion of disability to their communities in Israel. The project described, initiated and supported by an American NGO, provides a case for exploring how the secular notion of disability rights is cast and recast in a Muslim world of meaning. It focuses on the mediation strategy that I call modular translation, employed by imams in sermons delivered for the purpose of altering or improving the status and conditions of people with disabilities. This strategy, as it emerged from the analysis, entails decoupling norms of conduct from their underlying justifications. It thus suggests that norms of conduct are open to change so long as the believers' cosmology remains intact. As such, this turn may offer new avenues of thinking and acting about globalizing human rights within the arena of health and disability. © 2014 Springer Science+Business Media New York.


Benveniste Y.,Tel Aviv University
International Journal of Engineering Science | Year: 2013

Two models of three-dimensional thin interphases are formulated in the setting of steady thermal conduction and general curvilinear anisotropy. The models make possible to determine the fields in the media adjacent to the interphase without the need to solve for fields within the interphase itself. They facilitate the implementation of methods that are aimed at the determination of the effective moduli of heterogeneous media which contain thin interphases. A formulation of the so-called Effective Medium Approximation (EMA) in composite media is given in which we incorporate the developed interphase models. The implementation of the constructed general framework is illustrated for the special case of a composite material which consists of coated spherical particles that possess spherical transverse isotropy, and are embedded in an isotropic matrix. © 2013 Elsevier Ltd. All rights reserved.


Marx D.,Tel Aviv University
Proceedings of the Annual ACM Symposium on Theory of Computing | Year: 2010

An important question in the study of constraint satisfaction problems (CSP) is understanding how the graph or hypergraph describing the incidence structure of the constraints influences the complexity of the problem. For binary CSP instances (i.e., where each constraint involves only two variables), the situation is well understood: the complexity of the problem essentially depends on the treewidth of the graph of the constraints. However, this is not the correct answer if constraints with unbounded number of variables are allowed, and in particular, for CSP instances arising from query evaluation problems in database theory. Formally, if H is a class of hypergraphs, then let CSP(H) be CSP restricted to instances whose hypergraph is in H. Our goal is to characterize those classes of hypergraphs for which CSP(H) is polynomial-time solvable or fixed-parameter tractable, parameterized by the number of variables. In the applications related to database query evaluation, we usually assume that the number of variables is much smaller than the size of the instance, thus parameterization by the number of variables is a meaningful question. The most general known property of H that makes CSP(H) polynomial-time solvable is bounded fractional hypertree width. Here we introduce a new hypergraph measure called submodular width, and show that bounded submodular width of H (which is a strictly more general property than bounded fractional hypertree width) implies that CSP(H) is fixed-parameter tractable. In a matching hardness result, we show that if H has unbounded submodular width, then CSP(H) is not fixed-parameter tractable (and hence not polynomial-time solvable), unless the Exponential Time Hypothesis (ETH) fails. The algorithmic result uses tree decompositions in a novel way: instead of using a single decomposition depending on the hypergraph, the instance is split into a set of instances (all on the same set of variables as the original instance), and then the new instances are solved by choosing a different tree decomposition for each of them. The reason why this strategy works is that the splitting can be done in such a way that the new instances are "uniform" with respect to the number extensions of partial solutions, and therefore the number of partial solutions can be described by a submodular function. For the hardness result, we prove via a series of combinatorial results that if a hypergraph H has large submodular width, then a 3SAT instance can be efficiently simulated by a CSP instance whose hypergraph is H. To prove these combinatorial results, we need to develop a theory of (multicommodity) flows on hypergraphs and vertex separators in the case when the function b(S) defining the cost of separator S is submodular. © 2010 ACM.


Ruzin A.,Tel Aviv University
IEEE Transactions on Electron Devices | Year: 2012

This paper tackles the issue of downscaling of an ohmic contact from the infinite approximation to nanometer dimensions. Using the finite-element simulation program, it is shown that small-size ohmic contacts on a wide-bandgap semiconductor exhibit nonlinear current-voltage dependence in case velocity saturation is introduced. Furthermore, the dependence becomes asymmetrical around zero bias. In addition, it is shown that in small-size contacts, a nonlocal tunneling is bound to occur even in pure ohmic contacts. This may explain the absence of linear I- V curves in the reported experiments with nanometer-scale contacts. © 1963-2012 IEEE.


Beilis I.I.,Tel Aviv University
IEEE Transactions on Plasma Science | Year: 2013

A transient model of spot on a bulk cathode is developed, considering the initial adjacent plasma generated during arc triggering. A self-consistent approach is described and a closed mathematical solution is presented to understand the transient cathode phenomena and the time-dependent cathode potential drop (CPD), considering the kinetics and gas dynamics of the cathode plasma flow. The time-dependent spot development is calculated by considering different existing lifetimes τ of an initial plasma adjacent to the cathode for Cu, Cr, and W and 10-A spot current. The lifetime τ is in the range of 2-100 ns. The solution shows that for Cu, the cathode temperature increased from 3500 to 4300 K with spot time. The CPD decreased with spot time from initial values 100-45 V (depending on τ) to 14-15 V at steady state. The solution for a refractory W cathode is obtained using a previously developed virtual cathode model. Calculation shows that a spot current density of simrm 10-7 A cm2 can support the spot initiation in a time of 2 ns considering W cathode vaporization with plasma generation by atom ionization. When τ increased from 2 ns to the 2 μ s range, the W cathode temperature decreased from ∼ 10000 K to a relatively low level of 7500 K. © 1973-2012 IEEE.


Alsop G.I.,University of Aberdeen | Marco S.,Tel Aviv University
Journal of Structural Geology | Year: 2011

The Late Pleistocene Lisan Formation preserved next to the Dead Sea provides exceptional 3-D exposures of folds and faults generated during soft-sediment slumping and deformation. It is possible to generate a range of four different scenarios associated with overprinting in a single slump event. The progressive evolution of slump systems may be broadly categorised into initiation, translation, cessation, relaxation and compaction phases. Thrust packages typically define piggyback sequences during slump translation, with back-steepening of imbricate faults leading to collapse of folds back up the regional palaeoslope. Detailed evaluation of slumped horizons may also permit structures to be traced across apparently separate and distinct slumped units. The recognition that slumps may be reworked by younger seismically-triggered events suggests that in some cases the seismic recurrence interval may be shorter than previously anticipated. © 2011 Elsevier Ltd.


Kochman Y.,Massachusetts Institute of Technology | Zamir R.,Tel Aviv University
IEEE Transactions on Information Theory | Year: 2011

Analog (uncoded) transmission provides a simple and robust scheme for communicating a Gaussian source over a Gaussian channel under the mean-squared-error (MSE) distortion measure. Unfortunately, its performance is usually inferior to the all-digital, separation-based source-channel coding solution, which requires exact knowledge of the channel at the encoder. The loss comes from the fact that except for very special cases, e.g., white source and channel of matching bandwidth (BW), it is impossible to achieve perfect matching of source to channel and channel to source by linear means. We show that by combining prediction and modulo-lattice operations, it is possible to match any colored Gaussian source to any colored Gaussian noise channel (of possibly different BW), hence achieve Shannon's optimum attainable performance R(D)=C. Furthermore, when the source and channel BWs are equal (but otherwise their spectra are arbitrary), this scheme is asymptotically robust in the sense that for high signal-to-noise ratio (SNR) a single encoder (independent of the noise variance) achieves the optimum performance. The derivation is based upon a recent modulo-lattice modulation scheme for transmitting a Wyner-Ziv source over a dirty-paper channel. © 2011 IEEE.


Beilis I.I.,Tel Aviv University
Physics of Plasmas | Year: 2015

Experiments in the last decade showed that for cathode spots in a magnetic field that obliquely intercepts the cathode surface, the current per spot increased with the transverse component of the magnetic field and decreased with the normal component. The present work analyzes the nature of cathode spot splitting in an oblique magnetic field. A physical model for cathode spot current splitting was developed, which considered the relation between the plasma kinetic pressure, self-magnetic pressure, and applied magnetic pressure in a current carrying cathode plasma jet. The current per spot was calculated, and it was found to increase with the tangential component of the magnetic field and to decrease with the normal component, which agrees well with the experimental dependence. © 2015 AIP Publishing LLC.


Shavit N.,Tel Aviv University
Communications of the ACM | Year: 2011

The advent of multicore processors as the standard computing platform will force major changes in software design. © 2011 ACM.


Karliner M.,Tel Aviv University | Rosner J.L.,University of Chicago
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

We discuss the possible production and discovery channels in e+e- and pp machines of the Xb, the bottomonium counterpart of X(3872) and the putative isoscalar analogue of the charged bottomoniumlike states Zb discovered by Belle. We suggest that the Xb may be close in mass to the bottomonium state χb1(3P), mixing with it and sharing its decay channels, just as X(3872) is likely a mixture of a D¯D∗ molecule and χc1(2P). Consequently, the experiments which reported observing χb1(3P) might have actually discovered the Xb, or a mixture of the two states. © 2015 American Physical Society.


Barzilai A.,Tel Aviv University
Mechanisms of Ageing and Development | Year: 2011

A hallmark of neurodegenerative diseases is impairment of certain aspects of " brain functionality" , which is defined as the total input and output of the brain's neural circuits and networks. A given neurodegenerative disorder is characterized by affected network organization and topology, cell numbers, cellular functionality, and the interactions between neural circuits. Neuroscientists generally view neurodegenerative disorders as diseases of neuronal cells; however, recent advances suggest a role for glial cells and an impaired vascular system in the etiology of certain neurodegenerative diseases. It is now clear that brain pathology is, to a very great extent, pathology of neurons, glia and the vascular system as these determine the degree of neuronal death as well as the outcome and scale of the neurological deficit. This review article is focused on the intricate interrelations among neurons, glia, the vascular system, neuronal cells, and the DNA damage response. Here I describe various aspects of neural and glial cell fate and the vascular system in genomic instability disorders including ataxia telangiectasia (A-T) and Nijmegen breakage syndrome. © 2011.


Brin Y.S.,Tel Aviv University
International orthopaedics | Year: 2013

Anatomical reduction and fixation of unstable ankle fractures is necessary to prevent post-traumatic arthritis. Malunion of the distal fibula in unstable ankle fractures can lead to late degenerative changes of the ankle. Late reconstruction of the ankle can improve its function and postpone the need for ankle fusion or replacement. We discuss three patients who presented with fibular malunion. All developed medial gutter opening, syndesmotic widening, and lateral shift and/or talar tilt. Surgery involved an anteromedial approach to clean the medial gutter, an anterolateral approach to clean the syndesmotic interval, elongation of the fibula by six to eight millimetres and stabilisation with a cervical spine cage and a locked plate. After one year, all patients had radiologically demonstrated reduction of the talus in the mortise. Improved function was recorded at final follow up. The cage provides several advantages over other fixation methods, including osteoconductive properties, avoiding bone graft donor site morbidity, and the range of sizes allows the surgeon to adjust the amount of elongation. Using spinal cages to treat malunited fibula fractures has several advantages compared to bone graft and good results can be expected.


Ruvinov E.,Ben - Gurion University of the Negev | Leor J.,Tel Aviv University | Cohen S.,Ben - Gurion University of the Negev
Biomaterials | Year: 2011

Proper spatio-temporal delivery of multiple therapeutic proteins represents a major challenge in therapy strategies aimed at inducing myocardial regeneration after myocardial infarction (MI). We hypothesized that the dual delivery of insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF) by injectable affinity-binding alginate biomaterial would maximize their therapeutic effects, leading to a more favorable course of tissue restoration after acute MI. A sequential release of IGF-1 followed by HGF was attained from affinity-binding alginate biomaterial, which also protected the proteins from proteolysis (shown by mass spectroscopy). The released factors retained bioactivity, as judged by their capability to activate their respective signaling pathways and to prevent cardiomyocyte apoptosis in vitro. In a rat model of acute MI, an intramyocardial injection of the dual IGF-1/HGF affinity-bound alginate biomaterial preserved scar thickness, attenuated infarct expansion and reduced scar fibrosis after 4 weeks, concomitantly with increased angiogenesis and mature blood vessel formation at the infarct. Furthermore, this treatment prevented cell apoptosis, induced cardiomyocyte cell cycle re-entry and increased the incidence of GATA-4-positive cell clusters. The dual delivery of IGF-1 and HGF from affinity-binding alginate biomaterial represents a useful strategy to treat MI. It showed a marked therapeutic efficacy at various tissue levels, as well as potential to induce endogenous regeneration of cardiac muscle. © 2010 Elsevier Ltd.


Erez N.,Tel Aviv University
Nature Cell Biology | Year: 2016

The liver is the most common metastatic route of pancreatic cancer. Early recruitment of granulin-secreting inflammatory monocytes to the liver is now shown to reprogram hepatic stellate cells into myofibroblasts that modulate the liver microenvironment to support the growth of metastasizing tumour cells. © 2016 Macmillan Publishers Limited.


Streifler J.Y.,Tel Aviv University
Journal of Neural Transmission | Year: 2011

Asymptomatic significant (≥50%) carotid stenosis (ASCS) is a frequent finding in the aging population. The prevalence of moderate stenosis (50-70%) increases from 3.6% for those <70 years to 9.3% in those ≥70 years. The (additional) prevalence of severe (70-99%) stenosis is 1.7%. The natural history of ASCS is quite benign. The overall risk of stroke is around 2% per year and within the group higher degrees of stenosis are associated with higher risks. Yet this stroke risk also includes "unrelated" strokes (i.e., lacunar and cardioembolic), and similarly, it is more of a marker for identifying high-risk group of patients at risk of cardiovascular morbidity and mortality (as revealed by many studies)! Carotid endarterectomy (CEA) has been evaluated in several studies; mainly ACAS and ACST. An overall modest benefit of about 1% risk reduction (per year) was found for CEA (with a peri-operative risk of <3%) versus medical treatment, over a 5-year period. Basically these two studies recruited similar patients with ≥60% stenosis based on carotid duplex. However, the similar favorable results differ: while ACAS (published in 1995) found the risk for ipsilateral stroke in the medical group to be 11% over a 5-year period, the 11.8% risk observed in ACST (published in 2004) was for any strokes-showing a better "natural history" for patients with ASCS in the recent study. This observation adds to other reports suggesting a better outcome for patients with ASCS in the recent years, probably because of better medical treatment, mainly due to the significant increase in the use of statins. The suggested guideline that results from the above-mentioned studies is that CEA should be considered in every patient with significant (≥60%?, ≥70%?) stenosis who has a life expectancy of more than 5 years (and is <75 years?). Taking this advice as such, would mean that we should screen for ASCS and operate on all appropriate candidates. This will result in a surge of CEA's! Such a recommendation is not in place, because the observed benefit of CEA by numbers needed to treat (NNT) per year to prevent any stroke is more than one hundred! (for symptomatic patients NNT is <10). This high-figure (i.e., low yield) results from failure of these studies to identify specific risk-factors (including the degree of stenosis within the wide range [60-99%] allowed in the studies) in patients with ASCS. Some studies are underway. Therefore, at present, it seems that for most patients, best (intensive) medical treatment is the best option. Alternately, they should join studies that will help to identify patients with the highest risk-those who will clearly benefit from carotid intervention. © 2011 Springer-Verlag.


Invasive aspergillosis (IA) in neutropenic patients is characterized by angioinvasion, intravascular thrombosis and tissue infarction, features that lead to sequestration of infected tissue and impaired fungal clearance. Recent research has shown that host angiogenesis, the homeostatic compensatory response to tissue hypoxia, is downregulated by Aspergillus fumigatus secondary metabolites. A. fumigatus metabolites inhibit multiple key angiogenic mediators, notably basic FGF, VEGF and their respective receptors. Moreover, repletion of basic FGF and VEGF enhances angiogenesis at the site of infection, induces trafficking of polymorphonuclear leukocytes into fungal-infected tissue and enhances antifungal drug activity. This review summarizes the emerging roles of vasculopathy and angiogenesis in the pathogenesis of IA, emphasizing the importance of the underlying mode of immunosuppression. Modulation of angiogenesis is a potential target for novel therapeutic strategies against IA. © 2013 Future Medicine Ltd.


Natan A.,Tel Aviv University
Physical Chemistry Chemical Physics | Year: 2015

The calculation of Fock-exchange interaction is an important task in the computation of molecule and solid properties. In this work we describe how we implement the Fock exchange in the real-space formalism using the KLI approximation for the OEP equation for 3D periodic systems. The implementation is demonstrated within the PARSEC real-space pseudopotential code that uses a discrete uniform grid and norm conserving pseudopotentials for the ionic potentials. © 2015 the Owner Societies.


Erez U.,Tel Aviv University | Trott M.D.,Hewlett - Packard | Wornell G.W.,Massachusetts Institute of Technology
IEEE Transactions on Information Theory | Year: 2012

A rateless code-i.e., a rate-compatible family of codes-has the property that codewords of the higher rate codes are prefixes of those of the lower rate ones. A perfect family of such codes is one in which each of the codes in the family is capacity-achieving. We show by construction that perfect rateless codes with low-complexity decoding algorithms exist for additive white Gaussian noise channels. Our construction involves the use of layered encoding and successive decoding, together with repetition using time-varying layer weights. As an illustration of our framework, we design a practical three-rate code family. We further construct rich sets of near-perfect rateless codes within our architecture that require either significantly fewer layers or lower complexity than their perfect counterparts. Variations of the basic construction are also developed, including one for time-varying channels in which there is no a priori stochastic model. © 2011 IEEE.


Eliazar I.,Tel Aviv University
Annals of Physics | Year: 2015

Rank distributions are collections of positive sizes ordered either increasingly or decreasingly. Many decreasing rank distributions, formed by the collective collaboration of human actions, follow an inverse power-law relation between ranks and sizes. This remarkable empirical fact is termed Zipf's law, and one of its quintessential manifestations is the demography of human settlements - which exhibits a harmonic relation between ranks and sizes. In this paper we present a comprehensive statistical-physics analysis of rank distributions, establish that power-law and exponential rank distributions stand out as optimal in various entropy-based senses, and unveil the special role of the harmonic relation between ranks and sizes. Our results extend the contemporary entropy-maximization view of Zipf's law to a broader, panoramic, Gibbsian perspective of increasing and decreasing power-law and exponential rank distributions - of which Zipf's law is one out of four pillars. © 2015 Elsevier Inc.


Netzer H.,Tel Aviv University | Marziani P.,National institute for astrophysics
Astrophysical Journal | Year: 2010

We present a new analysis of the motion of pressure-confined, broad-line region (BLR) clouds in active galactic nuclei (AGNs) taking into account the combined influence of gravity and radiation pressure. We calculate cloud orbits under a large range of conditions and include the effect of column density variation as a function of location. The dependence of radiation pressure force on the level of ionization and the column density are accurately computed. The main results are as follows. (1) The mean cloud locations (rBLR) and line widths (FWHMs) are combined in such a way that the simple virial mass estimate, rBLR, FWHM2/G, gives a reasonable approximation to MBH even when radiation pressure force is important. The reason is that L/M rather than L is the main parameter affecting the planar cloud motion. (2) Reproducing the mean observed rBLR, FWHM, and line intensity of Hβ and CIV λ 1549 requires at least two different populations of clouds. (3) The cloud location is a function of both L 1/2 and L/M. Given this, we suggest a new approximation for r BLR which, when inserted into the BH mass equation, results in a new approximation for MBH. The new expression involves L1/2, FWHM, and two constants that are obtained from a comparison with available M-σ* mass estimates. It deviates only slightly from the old mass estimate at all luminosities. (4) The quality of the present black hole mass estimators depends, critically, on the way the present M-σ* AGN sample (29 objects) represents the overall population, in particular the distribution of L/LEdd. © 2010. The American Astronomical Society. All rights reserved.


Leibovici L.,Rabin Medical Center | Leibovici L.,Tel Aviv University
Clinical Microbiology and Infection | Year: 2013

There are convincing data to show that the consequences of a severe infection extend well beyond the first month following it. During the first year after severe sepsis or infection, the survival of sepsis patients is guarded compared with matched control groups. Their quality of life is impaired, and they suffer from rapid degradation in cognition and functional capacity. We could postulate three explanations for the long-term bad outcomes of severe infections and sepsis (or a combination of the three): (i) sepsis usually happens in the elderly and sick, and it causes deterioration in life expectancy and functional status as an acute, non-specific event; (ii) an interaction between specific mechanisms of sepsis and underlying disorders; or (iii) long-term complications directly related to infection. If the second or third explanations are true, then management of the original infection/sepsis might have an influence on long-term outcomes. Elderly survivors of severe infections should be carefully assessed for whether they need intermediate care for recuperation and re-conditioning when leaving hospital. We need prospective, observational studies to define which are the factors that most influence long-term outcomes, and especially management of the acute infection. The investigation of long-term outcomes in trials of treatment modalities for sepsis or severe infections should be encouraged. The true answer for whether one treatment is better than another in severe infections or sepsis lies in the people trajectory in the year following the infection, and not only on 4-6 weeks outcome. © 2013 The Authors. Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.


Beinart R.,Johns Hopkins University | Beinart R.,Tel Aviv University | Nazarian S.,Johns Hopkins University
Circulation | Year: 2013

The overall risk of clinically significant adverse events related to EMI in recipients of CIEDs is very low. Therefore, no special precautions are needed when household appliances are used. Environmental and industrial sources of EMI are relatively safe when the exposure time is limited and distance from the CIEDs is maximized. The risk of EMI-induced events is highest within the hospital environment. Physician awareness of the possible interactions and methods to minimize them is warranted.© 2013 American Heart Association, Inc.


Elinav E.,Weizmann Institute of Science | Peer D.,Laboratory of NanoMedicine | Peer D.,Tel Aviv University
ACS Nano | Year: 2013

Inflammatory bowel disease (IBD) has been extensively studied in the last four decades both in animal models and humans. The treatment options remain disappointing, nonspecific, and associated with multiple systemic adverse effects. In this Perspective, we highlight issues related to emerging nanotechnologies designed particularly for treatment and disease management of IBD and discuss potential therapeutic target options with novel molecular imaging modalities. © 2013 American Chemical Society.


Ison M.J.,University of Leicester | Quian Quiroga R.,University of Leicester | Fried I.,University of California at Los Angeles | Fried I.,Tel Aviv University
Neuron | Year: 2015

The creation of memories about real-life episodes requires rapid neuronal changes that may appear after a single occurrence of an event. How is such demand met by neurons in the medial temporal lobe (MTL), which plays a fundamental role in episodic memory formation? We recorded the activity of MTL neurons in neurosurgical patients while they learned new associations. Pairs of unrelated pictures, one of a person and another of a place, were used to construct a meaningful association modeling the episodic memory of meeting a person in a particular place. We found that a large proportion of responsive MTL neurons expanded their selectivity to encode these specific associations within a few trials: cells initially responsive to one picture started firing to the associated one but not to others. Our results provide a plausible neural substrate for the inception of associations, which are crucial for the formation of episodic memories. © 2015 The Authors.


Miller Y.,NCI Inc | Ma B.,SAIC | Nussinov R.,SAIC | Nussinov R.,Tel Aviv University
Chemical Reviews | Year: 2010

Experimental and computational studies of Aβ amyloids have suggested that for any given segment there are one or more preferred parallel and (or) antiparallel structural states. The preferred organizations of the Aβ fragments do not appear to present straight forward rules with respect to length, hydrophobicity, and charge. Because polymorphism is presented by different Aβ segments, clearly a combination of these segments would lead to polymorphic full-length Aβ, although the relative populations in the full sequence are likely to be different. How the Aβ peptides assemble and form toxic entities and what is the mechanism of toxicity are major questions that persist in Alzheimer research. Two types of models of the three-dimensional structures of Aβ oligomers have been reported from computational and experimental studies. Because metal ions can coordinate with different residues in each structural model, the variety of the morphologies can increase quickly.


Segal G.,Tel Aviv University
Methods in Molecular Biology | Year: 2013

Legionella pneumophila the causative agent of Legionnaires' disease, actively manipulates host cell processes to establish a replication niche inside host cells. The establishment of its replication niche requires a functional Icm/Dot type IV secretion system which translocates about 300 effector proteins into host cells during infection. Many of these effectors were first identified as effector candidates by several bioinformatic approaches, and these predicted effectors were later examined experimentally for translocation and a large number of which were validated as effector proteins. Here, I summarized the bioinformatic approaches that were used to identify these effectors. © 2013 Springer Science+Business Media New York.


Bergman D.J.,Tel Aviv University
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2014

An exact calculation of the local electric potential field ψ(r) in the quasistatic limit is described for the case of a point electric charge q in a two-constituent composite medium. In the case of an ε2, ε1, ε2 three-parallel-slab microstructure, where q is in the top ε2 layer and both ε2 layers are infinitely thick while the ε1 layer has a finite thickness L1, a perfect imaging of the point charge is expected if ε1=-ε2 is real [J. B. Pendry, Phys. Rev. Lett. 85, 3966 (2000)PRLTAO0031-900710.1103/PhysRevLett.85.3966; R. J. Blaikie and D. O. S. Melville, J. Opt. A 7, S176 (2005)JOAOF81464-425810.1088/1464-4258/7/2/023; U. Leonhardt, New J. Phys. 11, 093040 (2009)NJOPFM1367-263010.1088/1367-2630/11/9/ 093040]. Among our results we find that an infinite resolution image of the point charge q is only achievable if the actual charge is situated at a distance that is between L1/2 and L1 away from the ε1 layer. © 2014 American Physical Society.


Leitner Y.,Child Development Center | Leitner Y.,Tel Aviv University
Frontiers in Human Neuroscience | Year: 2014

Symptoms of attention deficit hyperactivity disorder (ADHD) and autistic spectrum disorder (ASD) often co-occur. The DSM-IV had specified that an ASD diagnosis is an exclusion criterion for ADHD, thereby limiting research of this common clinical co-occurrence. As neurodevelopmental disorders, both ASD and ADHD share some phenotypic similarities, but are characterized by distinct diagnostic criteria. The present review will examine the frequency and implications of this clinical co-occurrence in children, with an emphasis on the available data regarding pre-school age. The review will highlight possible etiologies explaining it, and suggest future research directions necessary to enhance our understanding of both etiology and therapeutic interventions, in light of the new DSM-V criteria, allowing for a dual diagnosis. © 2014 Leitner.


Hammel I.,Tel Aviv University
Journal of the Royal Society, Interface / the Royal Society | Year: 2013

The inventory of secretory granules along the plasma membrane can be viewed as maintained in two restricted compartments. The release-ready pool represents docked granules available for an initial stage of fast, immediate secretion, followed by a second stage of granule set-aside secretion pool, with significantly slower rate. Transmission electron microscopy ultra-structural investigations correlated with electrophysiological techniques and mathematical modelling have allowed the categorization of these secretory vesicle compartments, in which vesicles can be in various states of secretory competence. Using the above-mentioned approaches, the kinetics of single vesicle exocytosis can be worked out. The ultra-fast kinetics, explored in this study, represents the immediately available release-ready pool, in which granules bound to the plasma membrane are exocytosed upon Ca(2+) influx at the SNARE rosette at the base of porosomes. Formalizing Dodge and Rahamimoff findings on the effect of calcium concentration and incorporating the effect of SNARE transient rosette size, we postulate that secretion rate (rate), the number (X) of intracellular calcium ions available for fusion, calcium capacity (0 ≤ M ≤ 5) and the fusion nano-machine size (as measured by the SNARE rosette size K) satisfy the parsimonious M-K relation rate ≈ C × [Ca(2+)](min(X,M))e(-K/2).


Alsop G.I.,University of Aberdeen | Marco S.,Tel Aviv University
Journal of the Geological Society | Year: 2012

Although it has been tacitly assumed since the seminal work of Jones in the 1930s that slump folds bear a systematic and meaningful relationship to the slope upon which they were presumably created, there has in reality been very little attempt to objectively verify this association via the collection of regional slump data in a relatively controlled setting. The potential to walk around the intact Dead Sea Basin at c. 425 m below mean sea level provides a perhaps unparalleled opportunity to undertake such verification via the direct examination of slump fold relationships. The collection of slump data in this well-constrained environment, where the seismogenic trigger for slumping is established via earthquake records, and the palaeogeographical controls are also recognizable and clearly link to the present bathymetry and landscape, thereby permits an evaluation of the use of slump folds as indicators of palaeoslope. The Late Pleistocene Lisan Formation cropping out to the west of the Dead Sea contains superb examples of slump folds that systematically face (>95%) and verge (>90%) towards the east. This study employs and evaluates five statistical techniques, including a new mean axial-planar dip (MAD) method, to analyse relationships between the orientation of slump folds and palaeoslopes. We recognize for the first time that the direction of slumping inferred from slump folds and thrusts varies systematically along the entire c. 100 km length of the western Dead Sea Basin. SE-directed slumping is preserved in the north, easterly directed slumping in the central portion and NE-directed slumping at the southern end of the Dead Sea. They are interpreted to form part of a large-scale and newly recognized radial slump system directed towards the depocentre of the precursor to the Dead Sea, and to be triggered by earthquakes associated with seismicity along the Dead Sea Fault.


Michaelson D.M.,Tel Aviv University
Alzheimer's and Dementia | Year: 2014

Brain pathology of Alzheimer's diseases (AD) and the genetics of autosomal dominant familial AD have been the "lamp posts" under which the AD field has been looking for therapeutic targets. Although this approach still remains valid, none of the compounds tested to date have produced clinically meaningful results. This calls for developing complementary therapeutic approaches and AD targets. The allele ε4 of apolipoprotein E4 (APOE ε4), is the most prevalent genetic risk factor for sporadic AD, and is expressed in more than half of the AD patients. However, in spite of its genetic prominence, the allele APOE ε4 and its corresponding protein product apoE4 have been understudied. We presently briefly discuss the reasons underlying this situation and review newly developed AD therapeutic approaches that target apoE4 and which pave the way for future studies. © 2014 The Alzheimer's Association. All rights reserved.


Lieberman D.,University of Miami | Lobel T.,Tel Aviv University
Evolution and Human Behavior | Year: 2012

The natural experiments created by the Israeli Kibbutzim and Taiwanese minor marriages provide unique testing grounds for investigating the mechanisms governing sibling detection, inbreeding avoidance and kin-selected altruism. Here we present two studies conducted on the coreared peers of Israeli Kibbutzim. We examined how coresidence duration - a cue that would have indicated genetic relatedness in ancestral environments - impacts the development of kin-directed behaviors. In both studies, we found that coresidence duration predicts levels of altruism and sexual aversions directed toward peers. We also investigated the relationship between personal sexual aversions and moral attitudes relating to peer sexual behavior. The absence of norms proscribing sex between peers on the Kibbutz allows for a more tightly controlled investigation of this relationship. We found that total coresidence duration with opposite-sex peers predicts the intensity of moral wrongness associated with third-party peer sexual behavior, but not other behaviors, including sibling incest. More directly, we found that the summed sexual aversion felt toward all opposite-sex peers predicts levels of moral wrongness associated with third-party peer sex. Mediation analyses confirmed that personal sexual aversions mediate the relationship between coresidence duration and moral attitudes regarding peer sex. These results bolster Westermarck's original claims that childhood coresidence serves as a kinship cue, leading to greater sexual aversions and altruistic motivations, and that personal sexual aversions shape attitudes relating to third-party sexual behavior. © 2012 Elsevier Inc.


Eilam D.,Tel Aviv University
Neuroscience and Biobehavioral Reviews | Year: 2014

Of mice and men: Building blocks in cognitive mapping. NEUROSCI BIOBEHAV REV XX(X) XXX-XXX-Exploration is the process by which humans and other animals gather spatial information and construct some representation of unfamiliar environments, and then utilize this information for traveling in those environments. This survey presents similarities in the travel paths of rodents and humans, suggesting that these constitute an expression of similar underlying biobehavioral mechanisms. Emphasis is given to exploration in dark or large environments, which one cannot encompass at a glance, necessitating a gradual sector-by-sector exploration. This is compared with exploration of the relatively small laboratory testing environments, where a condensed form of exploration dominates. In both rodents and humans, exploration culminates in free traveling, which is mainly determined by the physical environment. For this phase, some principles of urban design in humans and a reminiscent impact of landmarks in test environments in animals are compared. Finally, it is suggested that animal spatial behavior could provide insights into the way that humans perceive and conceive urban environments, and that spatial cognition in different animals, including humans, rests on an evolutionary analogy (or even homology). © 2014 Elsevier Ltd.


Epstein Y.,Tel Aviv University | Roberts W.O.,University of Minnesota
Scandinavian Journal of Medicine and Science in Sports | Year: 2011

Heat stroke is defined as a condition in which body temperature is elevated to such a level that it becomes a noxious agent causing body tissue dysfunction and damage with a characteristic multi-organ clinical and pathological syndrome. Marked hyperthermia, usually above 40.5°C and associated encephalopathy, occurs after thermoregulation is subordinated to circulatory and metabolic demands and to the associated systemic inflammatory reaction. Exertional heat stroke is a function of both intrinsic and extrinsic modulators. Intrinsic modulators like genetics, fitness, acclimatization, illness, medications, and sleep quality can alter individual risk and outcomes, while extrinsic modulators like exercise intensity and duration, clothing and equipment, ambient temperature, relative humidity, and solar radiation can affect the group risk and outcomes. This review integrates the current theoretical and accepted knowledge of physiological alterations into one model that depicts a common pathway from heat stress to heat stroke. © 2011 John Wiley & Sons A/S.


Nanoscale tribology is an active and rapidly developing area of research that poses fundamental scientific questions that, if answered, may offer great technological potential in the fields of friction, wear, and lubrication. When considering nanoscale material's junctions, surface commensurability often plays a crucial rule in dictating the tribological properties of the interface. This Review surveys recent theoretical work in this area, with the aim of providing a quantitative measure of the crystal lattice commensurability at interfaces between rigid materials and relating it to the tribological properties of the junction. By considering a variety of hexagonal layered materials, including graphene, hexagonal boron nitride, and molybdenum disulfide, we show how a simple geometrical parameter, termed the "registry index" (RI), can capture the interlayer sliding energy landscape as calculated using advanced electronic structure methods. The predictive power of this method is further demonstrated by showing how the RI is able to fully reproduce the experimentally measured frictional behavior of a graphene nanoflake sliding over a graphite surface. It is shown that generalizations towards heterogeneous junctions and non-planar structures (e.g., nanotubes) provide a route for designing nanoscale systems with unique tribological properties, such as robust superlubricity. Future extension of this method towards nonparallel interfaces, bulk-material junctions, molecular surface diffusion barriers, and dynamic simulations are discussed. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Slone M.,Tel Aviv University | Shoshani A.,The Interdisciplinary Center
Journal of Traumatic Stress | Year: 2014

This cross-sectional study investigated relations between conflict exposure and psychiatric symptoms among 8,727 Jewish Israeli adolescents aged 12-17 years from 1998-2011. This 14-year span included periods of terrorism, missile attacks, wars, relocations, military operations, and relative quiet, reflecting a dynamically changing, primarily violent climate. Annual samples from the same cities, geographical regions, and schools throughout the country were assessed for personal political life events (PLE) exposure and for psychiatric symptoms using the Brief Symptom Inventory (BSI; Derogatis & Spencer, ). Data were divided into 8 exposure periods: (a) pre-Intifada 1998-2000, (b) Intifada peak 2001-2003, (c) Intifada recession 2004, (d) evacuation 2005, (e) missiles and the 2006 Lebanon war, (f) peak missiles 2006-2007, (g) Operation Cast Lead 2008-2009, and (h) global terrorism 2010-2011. Results confirmed a relation between type of exposure period, PLE exposure, and psychiatric symptoms. In addition, PLE exposure was positively correlated with psychiatric symptoms (β = .49). A moderating effect of gender on the relationship between PLE exposure and the psychiatric index was found, with elevated symptoms among females (β = .30). © 2014 International Society for Traumatic Stress Studies.


Skalka N.,Tel Aviv University
Oncogene | Year: 2016

The Wnt pathway has essential roles in cell proliferation, cell fate determination and tumorigenesis by regulating the expression of a wide range of target genes. As a core signaling cascade, the canonical Wnt pathway is regulated at different levels by numerous proteins. We have previously shown that carboxypeptidase E (CPE) is a novel regulator of the canonical Wnt signaling pathway. Here, we show that CPE and the Wnt3a ligand are co-secreted from cells. We show that although the C'-terminal Lys residue of Wnt3a is critical for its activity and is important for the effect of CPE on the Wnt pathway, CPE does not execute its effect by removing this Wnt3a residue. Interestingly, CPE through its N'-terminal sequence, forms aggregates with Wnt3a and possible endoplasmic reticulum (ER) stress leading to its loss of function. Together, our current results provide a mechanistic insight into the way CPE regulates the canonical Wnt signaling pathway.Oncogene advance online publication, 4 July 2016; doi:10.1038/onc.2016.173. © 2016 Macmillan Publishers Limited


Fridman E.,Tel Aviv University
Automatica | Year: 2010

This paper considers sampled-data control of linear systems under uncertain sampling with the known upper bound on the sampling intervals. Recently a discontinuous Lyapunov function method was introduced by using impulsive system representation of the sampled-data systems (Naghshtabrizi, Hespanha, & Teel, 2008). The latter method improved the existing results, based on the input delay approach via time-independent Lyapunov functionals. The present paper introduces novel time-dependent Lyapunov functionals in the framework of the input delay approach, which essentially improve the existing results. These Lyapunov functionals do not grow after the sampling times. For the first time, for systems with time-varying delays, the introduced Lyapunov functionals can guarantee the stability under the sampling which may be greater than the analytical upper bound on the constant delay that preserves the stability. We show also that the term of the Lyapunov function, which was introduced in the above mentioned reference for the analysis of systems with constant sampling, is applicable to systems with variable sampling. © 2009 Elsevier Ltd. All rights reserved.


Levinson A.,Tel Aviv University
Geophysical and Astrophysical Fluid Dynamics | Year: 2010

Global linear stability analysis of a self-similar solution describing the interaction of a relativistic shell with an ambient medium is performed. The solution is shown to be unstable to convective Rayleigh-Taylor modes having angular scales smaller than the causality scale. Longer wavelength modes are stable and decay with time. For modes of sufficiently large spherical harmonic degree l the dimensionless growth rate scales as √l/G{cyrillic}, where G{cyrillic} is the Lorentz factor of the shell. The instability commences at the contact interface separating the shocked ejecta and shocked ambient gas and propagates to the shocks. The reverse shock front responds promptly to the instability and exhibits rapidly growing distortions at early times. Propagation to the forward shock is slower, and it is anticipated that the region near the contact will become fully turbulent before the instability is communicated to the forward shock. The non-universality of the Blandford-McKee blast wave solution suggests that turbulence generated by the instability in the shocked ambient medium may decay slowly with time and may be the origin of magnetic fields over a long portion of the blast wave evolution. It is also speculated that the instability may affect the emission from the shocked ejecta in the early postprompt phase of gamma-ray bursts. © 2010 Taylor & Francis.


Kaasbjerg K.,Tel Aviv University | Thygesen K.S.,Technical University of Denmark | Jauho A.-P.,Technical University of Denmark
Physical Review B - Condensed Matter and Materials Physics | Year: 2013

We theoretically study the acoustic phonon limited mobility in n-doped two-dimensional MoS2 for temperatures T<100 K and high carrier densities using the Boltzmann equation and first-principles calculations of the acoustic electron-phonon (el-ph) interaction. In combination with a continuum elastic model, analytic expressions and the coupling strengths for the deformation potential and piezoelectric interactions are established. We furthermore show that the deformation potential interaction has contributions from both normal and umklapp processes and that the latter contribution is only weakly affected by carrier screening. Consequently, the calculated mobilities show a transition from a high-temperature μ∼T-1 behavior to a stronger μ∼T-4 behavior in the low-temperature Bloch-Grüneisen regime characteristic of unscreened deformation potential scattering. Intrinsic mobilities in excess of 105 cm2 V-1 s -1 are predicted at T<10 K and high carrier densities (nâ‰1011 cm-2). At 100 K, the mobility does not exceed ∼7×103 cm2 V-1 s-1. Our findings provide new and important understanding of the acoustic el-ph interaction and its screening by free carriers, and is of high relevance for the understanding of acoustic phonon-limited mobilities in general. © 2013 American Physical Society.


Blumenfeld Z.,Technion - Israel Institute of Technology | Katz G.,Tel Aviv University | Evron A.,Technion - Israel Institute of Technology
Annals of Oncology | Year: 2014

The late effects of cancer treatment have recently gained a worldwide interest among reproductive endocrinologists, oncologists, and all health-care providers, and the protection against iatrogenic infertility caused by chemotherapy assumes a high priority. Here, we summarize the case for and against using GnRH-agonist for fertility preservation and minimizing chemotherapy-induced gonadotoxicity. The rationale and philosophy supporting its use is that preventing premature ovarian failure (POF) is preferable to treating it, following the dictum: 'an ounce of prevention is worth a pound of cure'. Despite many publications on this subject, there are many equivocal issues necessitating summary. Until now, 20 studies (15 retrospective and 5 randomized, controlled trials) have reported on 1837 patients treated with GnRH-a in parallel to chemotherapy, showing a significant decrease in POF rate in survivors versus 9 studies reporting on 593 patients, with results not supporting GnRH-a use. Patients treated with GnRH-a in parallel to chemotherapy preserved their cyclic ovarian function in 91% of cases when compared with 41% of controls, with a pregnancy rate of 19-71% in the treated patients. Furthermore, seven meta-analyses have concluded that GnRH-a are beneficial and may decrease the risk of POF in survivors. However, controversy still remains regarding the efficiency of GnRH-a in preserving fertility. Since not all the methods involving fertility preservation are unequivocally successful and safe, these young patients deserve to be informed of all the various modalities to minimize gonadal damage and preserve ovarian function and future fertility. Combining several methods for a specific patient may increase the odds for minimally invasive fertility preservation. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


In cardiac tissue engineering approaches to treat myocardial infarction, cardiac cells are seeded within three-dimensional porous scaffolds to create functional cardiac patches. However, current cardiac patches do not allow for online monitoring and reporting of engineered-tissue performance, and do not interfere to deliver signals for patch activation or to enable its integration with the host. Here, we report an engineered cardiac patch that integrates cardiac cells with flexible, freestanding electronics and a 3D nanocomposite scaffold. The patch exhibited robust electronic properties, enabling the recording of cellular electrical activities and the on-demand provision of electrical stimulation for synchronizing cell contraction. We also show that electroactive polymers containing biological factors can be deposited on designated electrodes to release drugs in the patch microenvironment on demand. We expect that the integration of complex electronics within cardiac patches will eventually provide therapeutic control and regulation of cardiac function. © 2016 Nature Publishing Group


The present study investigates how the changing socioeconomic conditions in Russia and Ukraine affect the psychological well-being of high-school adolescents in these countries. Six indexes of psychological well-being, the adolescents' perception of the economic conditions in their families, perceived parental practices (care and autonomy providing), and perceived social support were measured in 1999 and 2007. Macro-level socioeconomic conditions in Russia and Ukraine, as well as the adolescents' perception of the economic conditions in their family, substantially improved from 1999 to 2007. However, the psychological well-being of the adolescents, as well as their perception of parental practices and the social support received from parents, peers, and teachers did not change. Russian adolescents consistently reported higher self-esteem and school competence than their Ukrainian peers, as well as higher parental care and autonomy providing, and higher social support received from peers. At the individual level, perceived parental care and autonomy providing, as well as perceived social support from parents, peers, and teachers were the major contributors to the adolescents' psychological well-being. The obtained results are discussed in light of the conservation of resources and ecological systems theories. © 2009 Springer-Verlag.


Jablonka E.,Tel Aviv University
Clinical Pharmacology and Therapeutics | Year: 2012

The biological and medical importance of epigenetics is now taken for granted, but the significance of one aspect of it- epigenetic inheritance-is less widely recognized. New data suggest that not only is it ubiquitous, but both the generation and the transmission of epigenetic variations may be affected by developmental conditions. Population studies, formal models, and research on genomic and ecological stresses all suggest that epigenetic inheritance is important in both micro- and macroevolutionary change.


Yovel G.,Tel Aviv University | Belin P.,University of Glasgow | Belin P.,University of Montreal | Belin P.,Aix - Marseille University
Trends in Cognitive Sciences | Year: 2013

Both faces and voices are rich in socially-relevant information, which humans are remarkably adept at extracting, including a person's identity, age, gender, affective state, personality, etc. Here, we review accumulating evidence from behavioral, neuropsychological, electrophysiological, and neuroimaging studies which suggest that the cognitive and neural processing mechanisms engaged by perceiving faces or voices are highly similar, despite the very different nature of their sensory input. The similarity between the two mechanisms likely facilitates the multi-modal integration of facial and vocal information during everyday social interactions. These findings emphasize a parsimonious principle of cerebral organization, where similar computational problems in different modalities are solved using similar solutions. © 2013 Elsevier Ltd.


Zohar E.,Max Planck Institute of Quantum Optics | Cirac J.I.,Max Planck Institute of Quantum Optics | Reznik B.,Tel Aviv University
Reports on Progress in Physics | Year: 2015

Can high-energy physics be simulated by low-energy, non-relativistic, many-body systems such as ultracold atoms? Such ultracold atomic systems lack the type of symmetries and dynamical properties of high energy physics models: in particular, they manifest neither local gauge invariance nor Lorentz invariance, which are crucial properties of the quantum field theories which are the building blocks of the standard model of elementary particles. However, it turns out, surprisingly, that there are ways to configure an atomic system to manifest both local gauge invariance and Lorentz invariance. In particular, local gauge invariance can arise either as an effective low-energy symmetry, or as an exact symmetry, following from the conservation laws in atomic interactions. Hence, one could hope that such quantum simulators may lead to a new type of (table-top) experiments which will be used to study various QCD (quantum chromodynamics) phenomena, such as the confinement of dynamical quarks, phase transitions and other effects, which are inaccessible using the currently known computational methods. In this report, we review the Hamiltonian formulation of lattice gauge theories, and then describe our recent progress in constructing the quantum simulation of Abelian and non-Abelian lattice gauge theories in 1 + 1 and 2 + 1 dimensions using ultracold atoms in optical lattices. © 2016 IOP Publishing Ltd.


Zisapel N.,Tel Aviv University
Expert Opinion on Emerging Drugs | Year: 2012

Introduction: Sleep is a vital neurochemical process involving sleep-promoting and arousal centers in the brain. Insomnia is a pervasive disorder characterized by difficulties in initiating or maintaining or non-refreshing (poor quality) sleep and clinically significant daytime distress. Insomnia is more prevalent in women and old age and puts sufferers at significant physical and mental health risks. This review summarizes published data on the current and emerging insomnia drug classes, rationale for development and associated risks/benefits. (Summary of Product Characteristics and Medline search on "hypnotic" or specific drug names and "Insomnia"). Areas covered: GABAA receptor modulators facilitate sleep onset and some improve maintenance but increase risk of dependence, memory, cognitive and psychomotor impairments, falls, accidents and mortality. Melatonin receptor agonists improve quality of sleep and/or sleep onset but response may develop over several days. They have more benign safety profiles and are indicated for milder insomnia, longer usage and (prolonged release melatonin) older patients. Histamine H-1 receptor antagonists improve sleep maintenance but their effects on cognition, memory and falls remain to be demonstrated. Late-stage pipeline orexin OX1/OX2 and serotonin 5HT2A receptor antagonists may hold the potential to address several unmet needs in insomnia pharmacotherapy but safety issues cast some doubts over their future. Expert opinion: Current and new insomnia drugs in the pipeline target different sleep regulating mechanisms and symptoms and have different tolerability profiles. Drug selection would ideally be based on improvement in the quality of patients' sleep, overall quality of life and functional status weighed against risk to the individual and public health. © 2012 Informa UK, Ltd.


Khananshvili D.,Tel Aviv University
Molecular Aspects of Medicine | Year: 2013

The SLC8 gene family encoding Na+/Ca2+ exchangers (NCX) belongs to the CaCA (Ca2+/Cation Antiporter) superfamily. Three mammalian genes (SLC8A1, SLC8A2, and SLC8A3) and their splice variants are expressed in a tissue-specific manner to mediate Ca2+-fluxes across the cell-membrane and thus, significantly contribute to regulation of Ca 2+-dependent events in many cell types. A long-wanted mitochondrial Na+/Ca2+ exchanger has been recently identified as NCLX protein, representing a gene product of SLC8B1. Distinct NCX isoform/splice variants contribute to excitation-contraction coupling, long-term potentiation of the brain and learning, blood pressure regulation, immune response, neurotransmitter and insulin secretion, mitochondrial bioenergetics, etc. Altered expression and regulation of NCX proteins contribute to distorted Ca2+-homeostasis in heart failure, arrhythmia, cerebral ischemia, hypertension, diabetes, renal Ca2+ reabsorption, muscle dystrophy, etc. Recently, high-resolution X-ray structures of Ca2+-binding regulatory domains of eukaryotic NCX and of full-size prokaryotic NCX have become available and the dynamic properties have been analyzed by advanced biophysical approaches. Molecular silencing/overexpression of NCX in cellular systems and organ-specific KO mouse models provided useful information on the contribution of distinct NCX variants to cellular and systemic functions under various pathophysiological conditions. Selective inhibition or activation of predefined NCX variants in specific diseases might have clinical relevance, although this breakthrough has not yet been realized. A better understanding of the underlying molecular mechanisms as well as the development of in vitro procedures for high-throughput screening of "drug-like" compounds may lead to selective pharmacological targeting of NCX variants. © 2012 Elsevier Ltd. All rights reserved.


Shamir R.,Tel Aviv University
Annals of Nutrition and Metabolism | Year: 2012

Introduction: In 2003, a thiamine-deficient soy infant formula was produced in Germany and marketed exclusively in Israel. Between October and November 2003, infants with encephalopathy were admitted to several intensive care units in Israel and were later diagnosed as suffering from thiamine deficiency. The soy formula consumed by these children was found to be the cause of these admissions. Methods: A Medline search using the terms 'thiamine deficiency' and 'formula' or 'feeding' without year limit identified relevant published data on that event. Newspapers from Israel were screened from November 2003 until April 2011. Results: On November 2003, 2-6% of infants in Israel consumed this formula. The consumption of this thiamine-deficient formula was associated with the death of 3 infants and with more than 20 infants manifesting neurologic damage. In this report, we summarize the chain of events, the neurologic outcome, and discuss the lessons needed to be learned from this sad event. Conclusions: Based on difficulties in diagnosis of subtle deficiencies, we suggest that apparent history of safe use is not a reliable source for establishing adequate intake. Infant formulae can be produced or imported only under stringent criteria with the manufacturer/importer having total responsibility for the product. Copyright © 2012 S. Karger AG.


Eisenberg E.,Tel Aviv University
Current Topics in Microbiology and Immunology | Year: 2012

The first discoveries of mammalian A-to-I RNA editing have been serendipitous. In conjunction with the fast advancement in sequencing technology, systematic methods for prediction and detection of editing sites have been developed, leading to the discovery of thousands of A-to-I editing sites. Here we review the state-of-the-art of these methods and discuss future directions. © 2011 Springer-Verlag Berlin Heidelberg.


Gozes I.,Tel Aviv University
Current Alzheimer research | Year: 2010

The current review discusses microtubules and tau in the healthy brain and move on to the underling pathology of Alzheimer's disease (AD) with emphasis on tau and neurofibrillary tangles. Tangles have been associated with cognitive dysfunction causing neurodegeneration in the absence of plaques. AD, the most abundant tauopathy is characterized by β-amyloid plaques and tau tangles. An abundance of tau inclusions, in the absence of β-amyloid deposits, defines Pick's disease (frontotemporal lobar degeneration), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and other diseases. Our own focused research is on activity-dependent neuroprtective protein (ADNP). Our findings show that ADNP-deficiency leads to tauopathy which is inhibited by the ADNP derived drug candidate, davunetide (originally known as NAP). The current review further describes tau as a potential diagnostic marker followed by drug candidates that are aimed at fighting tau pathology. A recent historical perspective is the final comment of the manuscript. This paper is not a comprehensive review of the literature rather it gives my own point of view in the face of many publications and a great unmet need for future therapeutics. It is hoped that davunetide, a most advanced drug in clinical development will rapidly advance as a first effective treatment for a number of brain disorders broadly categorized as frontotemporal dementia (FTD) and serve as a prototype for future therapeutic development toward modification and remedy of currently intractable neurodegenerative diseases.


Varol C.,Tel Aviv University | Mildner A.,Weizmann Institute of Science | Jung S.,Weizmann Institute of Science
Annual Review of Immunology | Year: 2015

Macrophages are myeloid immune cells that are strategically positioned throughout the body tissues, where they ingest and degrade dead cells, debris, and foreign material and orchestrate inflammatory processes. Here we review two major recent paradigm shifts in our understanding of tissue macrophage biology. The first is the realization that most tissue-resident macrophages are established prenatally and maintained through adulthood by longevity and self-renewal. Their generation and maintenance are thus independent from ongoing hematopoiesis, although the cells can be complemented by adult monocyte-derived macrophages. Second, aside from being immune sentinels, tissue macrophages form integral components of their host tissue. This entails their specialization in response to local environmental cues to contribute to the development and specific function of their tissue of residence. Factors that govern tissue macrophage specialization are emerging. Moreover, tissue specialization is reflected in discrete gene expression profiles of macrophages, as well as epigenetic signatures reporting actual and potential enhancer usage. © 2015 by Annual Reviews. All rights reserved.


Leibovitch I.,Tel Aviv University
Dermatologic Surgery | Year: 2010

Background Lower lid involutional entropion is a common eyelid pathology affecting the elderly population. Most of the reported surgical techniques are mainly based on a lateral tarsal strip anchored to the orbital rim. ObjectiveS To report the surgical outcome using a simple single-stitch lateral wedge technique to repair involutional lower entropion. Methods This single-surgeon, retrospective, noncomparative cases series included all patients with involutional lower eyelid entropion who were operated on using the lateral wedge technique. Results Fifty-eight eyelids of 52 patients (46 unilateral, 6 bilateral; 27 men, 25 women; age, mean 67±10; range 50-85) underwent surgical repair. Immediate resolution of entropion and associated ocular symptoms was achieved in 55 eyelids (94.9%). One case had postoperative ectropion that completely resolved spontaneously after 4 weeks, and one had wound dehiscence that healed completely without any intervention. Another patient had residual entropion that resolved after an additional surgical repair. No other cases of recurrence were noted during a mean follow-up period of 16 months (range 6-24 months). Conclusion This minimally invasive single-stitch lateral wedge technique is a simple and effective procedure for repairing involutional lower eyelid entropion and is associated with low recurrence and complication rates. Igal Leibovitch, MD, has indicated no significant interest with commercial supporters. © 2010 by the American Society for Dermatologic Surgery, Inc.


Weiss G.,Tel Aviv University
Mathematics of Control, Signals, and Systems | Year: 2010

We investigate two classes of time-varying well-posed linear systems. Starting from a time-invariant scattering-passive system, each of the time-varying systems is constructed by introducing a time-dependent inner product on the state space and modifying some of the generating operators. These classes of linear systems are motivated by physical examples such as the electromagnetic field around a moving object. To prove the well-posedness of these systems, we use the Lax-Phillips semigroup induced by a well-posed linear system, as in scattering theory. © Springer-Verlag London Limited 2010.


Weiss A.J.,Tel Aviv University
IEEE Transactions on Signal Processing | Year: 2011

The localization of a stationary transmitter using receivers mounted on fast moving platforms is considered. It is assumed that the transmitted radio signal is random with known statistics. The conventional approach is based on two steps. In the first step the time difference of arrival and the differential Doppler shift are measured and in the second step these measurements are used for geolocation. We advocate a direct position determination approach that proves to be more computationally efficient and more precise for weak signals than the conventional approach. The direct method is a single-step method that uses the same signals as the two-step approach but searches directly for the emitter position without first estimating intermediate parameters such as Doppler frequency and the time delay. A secondary but important result is a derivation of closed-form and compact expressions of the Cramér-Rao lower bound. All results are verified by Monte Carlo computer simulations. © 2011 IEEE.


Alon N.,Tel Aviv University
Proceedings - Annual IEEE Symposium on Foundations of Computer Science, FOCS | Year: 2010

We show that the minimum possible size of an ∈-net for point objects and line (or rectangle)-ranges in the plane is (slightly) bigger than linear in 1=∈. This settles a problem raised by Matoušek, Seidel and Welzl in 1990. © 2010 IEEE.


Korczyn A.D.,Tel Aviv University
Journal of Alzheimer's Disease | Year: 2012

There is widespread recognition in the urgency to understand the causes and mechanisms of senile dementia. Attempts to find cures for Alzheimer's disease (AD) have, however, failed so far, in spite of enormous investments, intellectual and financial. We therefore have to reconsider the problem from new angles. AD is regarded as a disease because of its clinical manifestations and underlying pathology. However, this combination does not define a disease but rather a syndrome, just like hepatic cirrhosis in which liver pathology causes metabolic changes, but which can result from many different etiologies. It is unlikely that attacking a downstream phenomenon, like apoptosis or amyloid-β accumulation, can cure AD, or prevent the progression of the disease. It is probable that senile dementia is the result of a combination of several processes, working differently in each person. Epidemiological studies have identified many risk factors for "senile dementia of the Alzheimer type", some genetic but most environmental and therefore modifiable. Thus, a concerted action to fight the dementia epidemic must be made by aggressive action against its risk factors, and this battle must begin in midlife, not in old age. © 2012-IOS Press and the authors. All rights reserved.


Peer D.,Tel Aviv University | Lieberman J.,Program in Cellular and Molecular Medicine
Gene Therapy | Year: 2011

Harnessing RNA interference using small RNA-based drugs has great potential to develop drugs designed to knock down expression of any disease-causing gene, thereby greatly expanding the universe of possible drug targets. However, delivering small RNAs into specific tissues and cells is still a hurdle. Here, we review recent progress in overcoming systemic, local and cellular barriers to RNA drug delivery, focusing on strategies for targeted uptake. © 2011 Macmillan Publishers Limited All rights reserved.


Nelson N.,Tel Aviv University
Biochimica et Biophysica Acta - Bioenergetics | Year: 2011

Because life on earth is governed by the second law of thermodynamics, it is subject to increasing entropy. Oxygenic photosynthesis, the earth's major producer of both oxygen and organic matter, is a principal player in the development and maintenance of life, and thus results in increased order. The primary steps of oxygenic photosynthesis are driven by four multi-subunit membrane protein complexes: photosystem I, photosystem II, cytochrome b 6f complex, and F-ATPase. Photosystem II generates the most positive redox potential found in nature and thus capable of extracting electrons from water. Photosystem I generates the most negative redox potential found in nature; thus, it largely determines the global amount of enthalpy in living systems. The recent structural determination of PSII and PSI complexes from cyanobacteria and plants sheds light on the evolutionary forces that shaped oxygenic photosynthesis. This newly available structural information complements knowledge gained from genomic and proteomic data, allowing for a more precise description of the scenario in which the evolution of life systems took place. This article is part of a Special Issue entitled: Regulation of Electron Transport in Chloroplasts. © 2010 Elsevier B.V. All rights reserved.


Marx D.,Tel Aviv University
Theory of Computing Systems | Year: 2011

The way the graph structure of the constraints influences the complexity of constraint satisfaction problems (CSP) is well understood for bounded-arity constraints. The situation is less clear if there is no bound on the arities. In this case the answer depends also on how the constraints are represented in the input. We study this question for the truth table representation of constraints. We introduce a new hypergraph measure adaptive width and show that CSP with truth tables is polynomial-time solvable if restricted to a class of hypergraphs with bounded adaptive width. Conversely, assuming a conjecture on the complexity of binary CSP, there is no other polynomial-time solvable case. Finally, we present a class of hypergraphs with bounded adaptive width and unbounded fractional hypertree width. © 2009 Springer Science+Business Media, LLC.


Bronstein M.M.,University of Lugano | Bronstein A.M.,Tel Aviv University
IEEE Transactions on Pattern Analysis and Machine Intelligence | Year: 2011

Recent works have shown the use of diffusion geometry for various pattern recognition applications, including nonrigid shape analysis. In this paper, we introduce spectral shape distance as a general framework for distribution-based shape similarity and show that two recent methods for shape similarity due to Rustamov and Mahmoudi and Sapiro are particular cases thereof. © 2006 IEEE.


Moss S.M.,Queen Mary, University of London | Wale C.,Queen Mary, University of London | Smith R.,American Cancer Society | Evans A.,University of Dundee | And 2 more authors.
The Lancet Oncology | Year: 2015

Background: Age-specific effects of mammographic screening, and the timing of such effects, are a matter of debate. The results of the UK Age trial, which compared the effect of invitation to annual mammographic screening from age 40 years with commencement of screening at age 50 years on breast cancer mortality, have been reported at 10 years of follow-up and showed no significant difference in mortality between the trial groups. Here, we report the results of the UK Age trial after 17 years of follow-up. Methods: Women aged 39-41 from 23 UK NHS Breast Screening Programme units years were randomly assigned by individual randomisation (1:2) to either an intervention group offered annual screening by mammography up to and including the calendar year of their 48th birthday or to a control group receiving usual medical care (invited for screening at age 50 years and every 3 years thereafter). Both groups were stratified by general practice. We compared breast cancer incidence and mortality by time since randomisation. Analyses included all women randomly assigned who could be traced with the National Health Service Central Register and who had not died or emigrated before entry. The primary outcome measures were mortality from breast cancer (defined as deaths with breast cancer coded as the underlying cause of death) and breast cancer incidence, including in-situ, invasive, and total incidence. Because there is an interest in the timing of the mortality effect, we analysed the results in different follow-up periods. This trial is registered, number ISRCTN24647151. Findings: Between Oct 14, 1990, and Sept 25, 1997, 160-921 participants were randomly assigned; 53-883 women in the intervention group and 106-953 assigned to usual medical care were included in this analysis. After a median follow-up of 17 years (IQR 16·8-18·8), the rate ratio (RR) for breast cancer mortality was 0·88 (95% CI 0·74-1·04) from tumours diagnosed during the intervention phase. A significant reduction in breast cancer mortality was noted in the intervention group compared with the control group in the first 10 years after diagnosis (RR 0·75, 0·58-0·97) but not thereafter (RR 1·02, 0·80-1·30) from tumours diagnosed during the intervention phase. The overall breast cancer incidence during 17 year follow-up was similar between the intervention group and the control group (RR 0·98, 0·93-1·04). Interpretation: Our results support an early reduction in mortality from breast cancer with annual mammography screening in women aged 40-49 years. Further data are needed to fully understand long-term effects. Cumulative incidence figures suggest at worst a small amount of overdiagnosis. Funding: National Institute for Health Research Health Technology Assessment programme and the American Cancer Society. Past funding was received from the Medical Research Council, Cancer Research UK, the UK Department of Health, and the US National Cancer Institute. © 2015 Elsevier Ltd.


White B.A.,Urbana University | Lamed R.,Tel Aviv University | Bayer E.A.,Weizmann Institute of Science | Flint H.J.,University of Aberdeen
Annual Review of Microbiology | Year: 2014

Mammals rely entirely on symbiotic microorganisms within their digestive tract to gain energy from plant biomass that is resistant to mammalian digestive enzymes. Especially in herbivorous animals, specialized organs (the rumen, cecum, and colon) have evolved that allow highly efficient fermentation of ingested plant biomass by complex anaerobic microbial communities. We consider here the two most intensively studied, representative gut microbial communities involved in degradation of plant fiber: those of the rumen and the human large intestine. These communities are dominated by bacteria belonging to the Firmicutes and Bacteroidetes phyla. In Firmicutes, degradative capacity is largely restricted to the cell surface and involves elaborate cellulosome complexes in specialized cellulolytic species. By contrast, in the Bacteroidetes, utilization of soluble polysaccharides, encoded by gene clusters (PULs), entails outer membrane binding proteins, and degradation is largely periplasmic or intracellular. Biomass degradation involves complex interplay between these distinct groups of bacteria as well as (in the rumen) eukaryotic microorganisms. Copyright © 2014 by Annual Reviews. All rights reserved.


Polterovich L.,Tel Aviv University
Communications in Mathematical Physics | Year: 2014