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The Hebrew University of Jerusalem is Israel's second-oldest university, after the Technion. The Hebrew University has three campuses in Jerusalem and one in Rehovot. The world's largest Jewish studies library is located on its Edmond J. Safra Givat Ram campus.The first Board of Governors included Albert Einstein, Sigmund Freud, Martin Buber, and Chaim Weizmann. Four of Israel's prime ministers are alumni of the Hebrew University. In the last decade, seven researchers and alumni of the University received the Nobel Prize and one was awarded the Fields Medal.According to the Academic Ranking of World Universities, the Hebrew University is the top university in Israel, overall the 59th-best university in the world, 16th in mathematics, 27th in computer science and 44th in business/economics.In 2013, the Center for World University Rankings ranked the Hebrew University 21st in the world and the top in Israel in its World University Rankings, while another survey ranked it as the 9th best university to work in, and the 2nd best outside of the United States. Wikipedia.

Barniol Duran R.,Hebrew University of Jerusalem
Monthly Notices of the Royal Astronomical Society | Year: 2014

Using gamma-ray burst (GRB) radio afterglow observations, we calculate the fraction of shocked plasma energy in the magnetic field in relativistic collisionless shocks (∈B). We obtained ∈B for 38 bursts by assuming that the radio afterglow light curve originates in the external forward shock, and that its peak at a few to tens of days is due to the passage of the minimum (injection) frequency through the radio band. This allows for the determination of the peak synchrotron flux of the external forward shock, fp, which is fp α ∈ 1/2 B . The obtained value of ∈B is conservatively a minimum if the time of the 'jet break' is unknown, since after the 'jet break' fp is expected to decay with time faster than before it. Claims of 'jet breaks' have been made for a subsample of 23 bursts, for which we can estimate a measurement of ∈B. Our results depend on the blast wave total energy, E, and the density of the circumstellar medium (CSM), n, as ∈B α E-2n-1. However, by assuming a CSM magnetic field (~10 μG), we can express the lower limits/measurements on ∈B as a density-independent ratio, B/Bsc, of the magnetic field behind the shock to the CSM shock-compressed magnetic field.We find that the distribution on both the lower limit on and the measurement of B/Bsc spans ~3.5 orders of magnitude and both have a median of B/Bsc ~ 30. This suggests that some amplification, beyond simple shock compression, is necessary to explain these radio afterglow observations. © 2014 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.

Van Der Meer J.R.,University of Lausanne | Belkin S.,Hebrew University of Jerusalem
Nature Reviews Microbiology | Year: 2010

Bacteria have long been the targets for genetic manipulation, but more recently they have been synthetically designed to carry out specific tasks. Among the simplest of these tasks is chemical compound and toxicity detection coupled to the production of a quantifiable reporter signal. In this Review, we describe the current design of bacterial bioreporters and their use in a range of assays to measure the presence of harmful chemicals in water, air, soil, food or biological specimens. New trends for integrating synthetic biology and microengineering into the design of bacterial bioreporter platforms are also highlighted. © 2010 Macmillan Publishers Limited. All rights reserved.

Zung A.,Hebrew University of Jerusalem
Pediatric diabetes | Year: 2012

Type 1 diabetes is an autoimmune disease occurring in genetically susceptible individuals. The precipitating cause is unclear. Recently, the Second Lebanon War exposed a large civilian population in northern Israel to significant psychological stress in the form of repeated barrages of missile attacks. We hypothesized that trends in regional incidence of type 1 diabetes before and after the war would reflect an association with stress. All type 1 diabetes patients aged 0-17 yr who were reported to the Israel Juvenile Diabetes Register (n = 1822) in the four pre-war (2002-2005) and two post-war years (2006-2007) were included in the study. The patients were stratified by gender, age, ethnicity, family history of type 1 diabetes, season at diagnosis, and region of residency, namely, those who lived in the northern regions that were attacked and those in other regions. The post-war incidence of type 1 diabetes was increased in the northern regions (rate ratio, RR = 1.27; p = 0.037), with no change in the other regions. This change was more prominent in males (RR = 1.55; p = 0.005) but similar in summer and winter, in different ages, and in different ethnic groups. There was no change in the proportion of new patients with a family history of the disease. For the first time in a large population, we found a positive association between the trauma of war and an increase in the incidence of type 1 diabetes in children and adolescents. The increase in incidence was not associated with genetic susceptibility to the disease. © 2011 John Wiley & Sons A/S.

Shalev-Shwartz S.,Hebrew University of Jerusalem | Tewari A.,University of Texas at Austin
Journal of Machine Learning Research | Year: 2011

We describe and analyze two stochastic methods for l1 regularized loss minimization problems, such as the Lasso. The first method updates the weight of a single feature at each iteration while the second method updates the entire weight vector but only uses a single training example at each iteration. In both methods, the choice of feature or example is uniformly at random. Our theoretical runtime analysis suggests that the stochastic methods should outperform state-of-the-art deterministic approaches, including their deterministic counterparts, when the size of the problem is large. We demonstrate the advantage of stochastic methods by experimenting with synthetic and natural data sets.1. © 2011 Shai Shalev-Shwartz and Ambuj Tewari.

Marcus Y.,Hebrew University of Jerusalem
Journal of Chemical Thermodynamics | Year: 2012

Properties of the guanidinium cation, GuH +=C(NH 2)3+, CAS registry 43531-41-5, were calculated from literature data that were critically examined. The following values are valid for T = 298.15 K and 100 kPa. For the isolated cation (in the ideal gas phase), the molar quantities are: enthalpy of formation, Δ fH° = (462 ± 3) kJ·mol -1, enthalpy increment H°- H0 = 14.22 kJ·mol -1, constant pressure heat capacity CP = 77.89 J·K -1·mol -1, entropy S°= 264.54 J·K·mol -1, and Gibbs free energy function -(G°- H0)/T = 216.94 J·K -1·mol -1. Values for the ion derived from data in aqueous solutions are the radius, r = (0.21 ± 0.02) nm, the surface charge density σ = 0.286 C·m -2, and polarizability α=4.44×10 -30m 3. Standard molar values for the aqueous ion are: enthalpy of formation Δ fH∞ = -(140 ± 7) kJ·mol -1, entropy S∞ = (201 ± 7) J·K -1·mol -1, heat capacity CP∞ = (103 ± 14) J·K -1·mol -1, volume V∞ = (46.3 ± 3.3) cm 3·mol -1, electrostriction volume Δ electrV∞ ∼ 0, refraction RD∞ = 11.21 cm 3·mol -1, conductivity λ∞ ∼ 39.6 S·cm 2·mol -1, self-diffusion coefficient D∞=1.06×10 -9m 2·s -1, viscosity B-coefficient B η = (0.058 ± 0.006) dm 3·mol -1, dielectric decrement d r/dc = -10.0 dm 3·mol -1 (chloride salt), and surface tension decrement dγ/dc = (0.04 ± 0.20) dm 3·mol -1. Standard molar values derived from a combination of the data for the gaseous and aqueous ions are the enthalpy of hydration Δ hydrH∞ = -(602 ± 8) kJ·mol -1, entropy of hydration Δ hydrS∞ = -63.7 J·K -1·mol -1, and the structural entropy Δ structS∞ = 83 J·K -1·mol -1. © 2011 Elsevier Ltd. All rights reserved.

Marcus Y.,Hebrew University of Jerusalem
Journal of Molecular Liquids | Year: 2012

The excess partial molar isobaric heat capacity of water, C PW E, in water-rich mixtures with co-solvents has been calculated. When the excitation of internal modes of the water molecules is deducted in part, the remainder indicates, if positive, that the relative extent of fully hydrogen bonded domains of the water is enhanced. This was demonstrated in the cases of aqueous methanol, ethanol, 1- and 2-propanol, t-butanol, 2-methoxyethanol, 1,2-dimethoxyethane, tetrahydrofuran, acetone, N,N-dimethylformamide, and N,N-dimethylacetamide. Some solutes such as ethylene glycol, 1,4-dioxane, acetonitrile, N-methylformamide, formamide (and urea), ethanolamine, and dimethylsulfoxide, many of which hydrogen-bond very strongly with water, do not enhance the water structure according to this criterion. The results are compared qualitatively with conclusions from the partial molar excess volumes of the solutions and these agree with the present ones. © 2011 Elsevier B.V. All rights reserved.

Zimran A.,Hebrew University of Jerusalem
Blood | Year: 2011

This review presents a cohesive approach to treating patients with Gaucher disease. The spectrum of the clinical presentation of the disease is broad, yet heretofore there was only one diseasespecific treatment. In the past 2 years, a global shortage of this product has resulted in reassessment of the "one enzyme-one disease-one therapy" mantra. It has also showcased the multiple levels that engage the patient, the treating physician, and the third-party insurer in providing adequate treatment to all symptomatic patients. The key points summarizing the way I manage my patients include accurate enzymatic diagnosis with mutation analysis (for some prognostication and better carrier detection in the family), a detailed follow-up every 6-12 months (with an option to see consultants and attention to comorbidities), and initiation of enzyme replacement therapy according to symptoms or deterioration in clinically significant features or both. I do not treat patients with very mild disease, but I consider presymptomatic therapy for patients at risk, including young women with poor obstetric history. I prefer the minimal-effective dose rather than the maximally tolerated dose, and when the difference between high-dose and lower-dose regimens is (merely statistically significant but) clinically meaningless, minimizing the burden on society by advocating less-expensive treatments is ethically justified. © 2011 by The American Society of Hematology.

Herber R.H.,Hebrew University of Jerusalem
Journal of Organometallic Chemistry | Year: 2012

Two structurally related organometallic compounds containing both Fe and Sn have been examined by temperature-dependent Mössbauer effect (ME) spectroscopy to elucidate the bonding and lattice dynamics of the metal atoms. The iron atom parameters are not otherwise remarkable and the motion is essentially isotropic in the temperature range 90 < T < 250 K and in good agreement with the corresponding X-ray data. In the case of the Sn resonances, there is a marked difference in the QS parameter of the two differing tin atoms, and in addition there is a significant difference in the vibrational data extracted from the ME studies and the X-ray derived values. The vibrational amplitudes of all metal atoms are compared and discussed. © 2012 Elsevier B.V. All rights reserved.

Feitelson E.,Hebrew University of Jerusalem
Water Policy | Year: 2012

In the modernist era, water is discussed as a single substance which has multiple uses. I argue that from a normative perspective water should be discussed in the plural term ('waters'), as they constitute a variety of 'things' with a similar chemical composition. Waters are composed of multiple 'needs', which are uses with a normative rationale, and of 'wants', which are desires that should be seen as economic demands. Moreover, waters should also be differentiated by source: natural, recycled or produced. This new language of water has direct policy implications. Needs, differentiated into direct human needs, spiritual needs, environmental needs and community needs, which may be prioritized, should be supplied regardless of cost considerations. 'Wants' and produced water should be priced at the full social cost of supply. Hence, while the rates at which needs are supplied should be determined by affordability, regardless of spatial differentiation in supply cost, the pricing of water supplied for 'wants' will vary over space. Thus water which is supplied through the same pipe to the same house may be subject to different pricing logics. However, there are many nuances to these generalizations, which have still to be fleshed out. © IWA Publishing & the Botín Foundation 2012.

Krumholz M.R.,University of California at Santa Cruz | Dekel A.,Hebrew University of Jerusalem
Monthly Notices of the Royal Astronomical Society | Year: 2010

We investigate the effects of radiation pressure from stars on the survival of the star-forming giant clumps in high-redshift massive disc galaxies, during the most active phase of galaxy formation. The clumps, typically of mass and radius are formed in the turbulent gas-rich discs by violent gravitational instability and then migrate into a central bulge in ∼10 dynamical times. We show that the survival or disruption of these clumps under the influence of stellar feedback depends critically on the rate at which they form stars. If they convert a few per cent of their gas mass to stars per free-fall time, as observed for all local star-forming systems and implied by the Kennicutt-Schmidt law, they cannot be disrupted. Only if clumps convert most of their mass to stars in a few free-fall times can feedback produce significant gas expulsion. We consider whether such rapid star formation is likely in high-redshift giant clumps. © 2010 The Authors. Journal compilation © 2010 RAS.

Recent prospective studies have shown that gestational stress in humans is more likely to cause cognitive and emotional problems in the offspring if it occurs during weeks 1220 of pregnancy. There are also suggestions that such problems may be gender dependent. This review describes recent studies that found sex differences in the behaviour and brain morphology of rats stressed prenatally during the equivalent period of neuronal development in humans. Learning deficits are more prevalent in males and anxious behaviour in females but their appearance depends also on the timing and intensity of the stress and the age when the offspring were tested. Cognitive deficits and anxiety are linked to a sex-dependent reduction in neurogenesis and in measures of dendritic morphology in the prefrontal cortex and hippocampal formation. Maternal adrenalectomy prior to the stress prevents the anxiety in both sexes and learning deficits in males. Corticosterone administration to the dam to mimic levels induced by stress reinstates only the anxiety, indicating that it arises from foetal exposure to corticosterone from the maternal circulation. Learning deficits in males may result from a combination of a reduction in testosterone and in aromatase activity, together with the action of other adrenal hormones. © 2011 Informa Healthcare USA, Inc.

Rollion-Bard C.,University of Lorraine | Erez J.,Hebrew University of Jerusalem
Geochimica et Cosmochimica Acta | Year: 2010

The boron isotope composition of marine carbonates is considered to be a seawater pH proxy. Nevertheless, the use of δ11B has some limitations such as the knowledge of the fractionation factor (α4-3) between boric acid and the borate ion and the amplitude of "vital effects" on this proxy that are not well constrained. Using secondary ion mass spectrometry (SIMS) we have examined the internal variability of the boron isotope ratio in the shallow water, symbionts bearing foraminiferan Amphistegina lobifera. Specimens were cultured at constant temperature (24 ± 0.1 °C) in seawater with pH ranging between 7.90 and 8.45. Intra-shell boron isotopes showed large variability with an upper limit value of ≈30‰. Our results suggest that the fractionation factor α4-3 of 0.97352 (Klochko et al., 2006) is in better agreement with our experiments and with direct pH measurements in seawater vacuoles associated with the biomineralization process in these foraminifera. Despite the large variability of the skeletal pH values in each cultured specimen, it is possible to link the lowest calculated pH values to the experimental culture pH values while the upper pH limit is slightly below 9. This variability can be interpreted as follows: foraminifera variably increase the pH at the biomineralization site to about 9. This increase above ambient seawater pH leads to a range in δ11B (Δ11B) for each seawater pH. This Δ11B is linearly correlated with the culture seawater pH with a slope of -13.1 per pH unit, and is independent of the fractionation factor α4-3, or the δ11Bsw through time. It may also be independent of the pKB (the dissociation constant of boric acid) value. Therefore, Δ11B in foraminifera can potentially reconstruct paleo-pH of seawater. © 2009 Elsevier Ltd. All rights reserved.

Kidron G.J.,Hebrew University of Jerusalem
Journal of Hydrology | Year: 2015

Following frequent droughts in the last 19. years, high mortality of perennial plants was noted in the Hallamish dune field in the Negev Desert (P= 95. mm). To evaluate the vegetation change, vegetation cover and species composition were studied in 20 plots located at the semi-stable non-crusted dune crest (CR) and 20 plots located at the crusted interdune (ID) during the summer of 2012 and compared to data from 1994. In addition, periodical moisture measurements were carried out in a pair of plots, 50-100. m apart, at CR and ID between October 2009 and September 2012. The findings exhibit a substantial decrease in the living perennials (mainly consisting of shrubs), with ID exhibiting the highest reduction in living shrubs. The findings are in agreement with measurements of the available water content, AWC (i.e., above the wilting point) during 2010-2012. While being recorded at >60. cm at CR, AWC was not recorded at ID at 60-120. cm depth during the summer months. Lower evaporation rates due to higher albedo and especially subsurface flow from the adjacent highly active crest are mainly seen responsible for deeper infiltration and higher AWC at CR. It is concluded that while sufficient AWC was present at CR to sustain most of the perennial shrubs also during frequent drought years, insufficient moisture was retained at ID to sustain most perennials. Non-crusted dune crests may thus serve as preferential habitats (fertility belts) for perennial plants, providing refugia for shrubs during frequent drought years. © 2015 Elsevier B.V.

Lensky I.M.,Bar - Ilan University | Dayan U.,Hebrew University of Jerusalem
Bulletin of the American Meteorological Society | Year: 2011

A method that enables the classification of topoclimatic regions from satellite remote sensing that have implications for ecology, agriculture, and epidemiology of vector-borne diseases, was examined. The time series of Earth-observing satellites (EOS) data was analyzed and the products of the analysis were used in order to identify topoclimatic features and their locations. The freely available preprocessed 8-day average clear-sky Land Surface Temperature (LST) product from the MODerate resolution imaging Spectroradiometer (MODIS) on NASA's TERRA satellite was used. A 10-yr time series (2000-09) of the LST product over northern Israel, along the East Mediterranean coast, and applied Temporal Fourier Analysis (TFA) to these time series was constructed. Predicting the timing of pest population expansion depends on the climate spatial variability induced by local topography, and can be used to time scouting efforts and pesticide applications.

Knafo A.,Hebrew University of Jerusalem | Jaffee S.R.,University of Pennsylvania | Jaffee S.R.,Kings College London
Development and Psychopathology | Year: 2013

Modern research acknowledges that psychopathology and individual differences in normal development are the joint products of both biological and social influences. Although there have been numerous publications on Gene & times; Environment interactions in the past decade, gene-environment correlation is another important form of gene-environment interplay that has received less attention. This Special Section demonstrates, using a range of methodological approaches, the importance of gene-environment correlation in developmental psychopathology. Several types of gene-environment correlation are described, including passive, evocative, and active. Other studies highlight the potential for gene-environment correlation to obscure associations between risk exposures and child psychopathology. Future directions for gene-environment correlation research are discussed. © 2013 Cambridge University Press.

Brooks A.M.,University of Wisconsin - Madison | Zolotov A.,Rutgers University | Zolotov A.,Hebrew University of Jerusalem
Astrophysical Journal | Year: 2014

We use high-resolution cosmological simulations of Milky Way (MW) mass galaxies that include both baryons and dark matter (DM) to show that baryonic physics (energetic feedback from supernovae and subsequent tidal stripping) significantly reduces the DM mass in the central regions of luminous satellite galaxies. The reduced central masses of the simulated satellites reproduce the observed internal dynamics of MW and M31 satellites as a function of luminosity. We use these realistic satellites to update predictions for the observed velocity and luminosity functions of satellites around MW-mass galaxies when baryonic effects are accounted for. We also predict that field dwarf galaxies in the same luminosity range as the MW classical satellites should not exhibit velocities as low as the satellites because the field dwarfs do not experience tidal stripping. Additionally, the early formation times of the satellites compared to field galaxies at the same luminosity may be apparent in the star formation histories of the two populations. Including baryonic physics in cold dark matter (CDM) models naturally explains the observed low DM densities in the MWs dwarf spheroidal population. Our simulations therefore resolve the tension between kinematics predicted in CDM theory and observations of satellites, without invoking alternative forms of DM. © 2014. The American Astronomical Society. All rights reserved.

Sharon G.,Galilee College | Oron M.,Hebrew University of Jerusalem
Quaternary International | Year: 2014

The lithic assemblage excavated from the Mousterian site of Nahal Mahanayeem Outlet (NMO) enables us to reconstruct a brief moment in the life of the Middle Palaeolithic hunter. The site, located on the eastern bank of the Jordan River at its outflow south from the Hula Valley, is a short-term, task specific hunting location at the shore of the Paleo-Hula Lake. Dated by OSL to ca. 65,000 years ago, the site has yielded a small assemblage of flint artifacts alongside exceptionally well-preserved animal bones and botanical remains. While only some 1000 artifacts have been counted, the lithic assemblage has the highest percentage of tools ever recorded in a Levantine Mousterian site. The primary lithic groups represented are pointed elements (over 10% of the entire assemblage) and cutting tools (over 5%). Other tool types typical of Mousterian sites, such as scrapers, are either absent or represented in very small numbers. The uniqueness of the assemblage is further highlighted by refitted sequences that, when combined with technological observations, suggest a non-Levallois, "blade-core like" reduction sequence. The NMO assemblage represents the tool kit used for the hunting and butchering of large mammals by a group of Levantine Mousterian hunters. It enables us to explore what tool types were selected for slaughtering and carcass processing, which tools were brought to the site and which were produced on site, what tools were left behind, and much more. The site was inhabited for a very short period, providing an opportunity to study hunting practices and human life ways in a resolution rarely possible for Late Pleistocene sites. © 2013 Elsevier Ltd and INQUA.

Yirmiya N.,Hebrew University of Jerusalem | Charman T.,Institute of Education
Journal of Child Psychology and Psychiatry and Allied Disciplines | Year: 2010

Autism is one of the most heritable neurodevelopmental conditions and has an early onset, with symptoms being required to be present in the first 3 years of life in order to meet criteria for the 'core' disorder in the classification systems. As such, the focus on identifying a prodrome over the past 20 years has been on pre-clinical signs or indicators that will be present very early in life, certainly in infancy. A number of novel lines of investigation have been used to this end, including retrospective coding of home videos, prospective population screening and 'high risk' sibling studies; as well as the investigation of pre- and peri-natal, brain developmental and other biological factors. While no single prodromal sign is expected to be present in all cases, a picture is emerging of indicative prodromal signs in infancy and initial studies are being undertaken to attempt to ameliorate early presentation and even 'prevent' emergence of the full syndrome. © 2010 The Authors. Journal compilation © 2010 Association for Child and Adolescent Mental Health.

Khelashvili G.,New York Medical College | Harries D.,Hebrew University of Jerusalem
Journal of Physical Chemistry B | Year: 2013

Although there have been great advances in understanding the effect of cholesterol on various properties of lipid membranes, its mechanistic role in determining the elasticity of bilayers at the molecular level is not fully resolved. Indeed, to date the molecular mechanisms that drive the experimentally detected differences in properties of saturated and unsaturated lipid bilayers that contain cholesterol remain unclear. By quantifying the cholesterol orientational degrees of freedom from atomistic molecular dynamics simulations of mixed lipid-cholesterol membranes, we address this question from the perspective of cholesterol tilt and splay. Following the fluctuations in orientations of cholesterol and of lipid molecules in simulations, we have extracted tilt and splay moduli both for cholesterol molecules and hydrocarbon lipid tails. This has further allowed us to estimate the contributions of these modes to the response of membranes to elastic deformations. We find that tilt and splay deformations importantly contribute to the overall elasticity of the mixed lipid membranes, and that they can account for the experimentally established differences between the liquid ordered sphingomyelin (SM)/cholesterol bilayers and fluid dioleoylphosphocholine (DOPC)/cholesterol bilayers. These findings underscore the importance of tilt and splay moduli, derived from simulations with relative computational ease, as useful metrics for quantitatively characterizing the mechanical properties of mixed lipid-cholesterol bilayers. © 2013 American Chemical Society.

Seligmann H.,University of Oslo | Seligmann H.,Hebrew University of Jerusalem
Biology Direct | Year: 2010

Background: The hypothesis that both mitochondrial (mt) complementary DNA strands of tRNA genes code for tRNAs (sense-antisense coding) is explored. This could explain why mt tRNA mutations are 6.5 times more frequently pathogenic than in other mt sequences. Antisense tRNA expression is plausible because tRNA punctuation signals mt sense RNA maturation: both sense and antisense tRNAs form secondary structures potentially signalling processing. Sense RNA maturation processes by default 11 antisense tRNAs neighbouring sense genes. If antisense tRNAs are expressed, processed antisense tRNAs should have adapted more for translational activity than unprocessed ones. Four tRNA properties are examined: antisense tRNA 5' and 3' end processing by sense RNA maturation and its accuracy, cloverleaf stability and misacylation potential.Results: Processed antisense tRNAs align better with standard tRNA sequences with the same cognate than unprocessed antisense tRNAs, suggesting less misacylations. Misacylation increases with cloverleaf fragility and processing inaccuracy. Cloverleaf fragility, misacylation and processing accuracy of antisense tRNAs decrease with genome-wide usage of their predicted cognate amino acid.Conclusions: These properties correlate as if they adaptively coevolved for translational activity by some antisense tRNAs, and to avoid such activity by other antisense tRNAs. Analyses also suggest previously unsuspected particularities of aminoacylation specificity in mt tRNAs: combinations of competition between tRNAs on tRNA synthetases with competition between tRNA synthetases on tRNAs determine specificities of tRNA amino acylations. The latter analyses show that alignment methods used to detect tRNA cognates yield relatively robust results, even when they apparently fail to detect the tRNA's cognate amino acid and indicate high misacylation potential.Reviewers: This article was reviewed by Dr Juergen Brosius, Dr Anthony M Poole and Dr Andrei S Rodin (nominated by Dr Rob Knight). © 2010 Seligmann; licensee BioMed Central Ltd.

Shalev-Shwartz S.,Hebrew University of Jerusalem | Zhang T.,Rutgers University
Journal of Machine Learning Research | Year: 2013

Stochastic Gradient Descent (SGD) has become popular for solving large scale supervised machine learning optimization problems such as SVM, due to their strong theoretical guarantees. While the closely related Dual Coordinate Ascent (DCA) method has been implemented in various software packages, it has so far lacked good convergence analysis. This paper presents a new analysis of Stochastic Dual Coordinate Ascent (SDCA) showing that this class of methods enjoy strong theoretical guarantees that are comparable or better than SGD. This analysis justifies the effectiveness of SDCA for practical applications. © 2013 Shalev-Shwartz and Zhang.

Oren A.,Hebrew University of Jerusalem
Current Opinion in Biotechnology | Year: 2015

Use of culture-independent studies have greatly increased our understanding of the microbiology of hypersaline lakes (the Dead Sea, Great Salt Lake) and saltern ponds in recent years. Exciting new information has become available on the microbial processes in Antarctic lakes and in deep-sea brines. These studies led to the recognition of many new lineages of microorganisms not yet available for study in culture, and their cultivation in the laboratory is now a major challenge. Studies of the metabolic potentials of different halophilic microorganisms, Archaea as well as Bacteria, shed light on the possibilities and the limitations of life at high salt concentrations, and also show their potential for applications in bioremediation. © 2015 Elsevier Ltd.

Sonin E.B.,Hebrew University of Jerusalem
Physical Review B - Condensed Matter and Materials Physics | Year: 2012

This paper studies the dynamics of twisted vortex bundles, which were detected in experimental investigations of superfluid turbulence in superfluid 3He-B. The analysis shows that a linear torsion oscillation of a vortex bundle is a particular case of the slow vortex mode related with the inertial wave, which was already investigated in the past in connection with observation of the Tkachenko waves in superfluid 4He and the experiments on the slow vortex relaxation in superfluid 3He-B. This paper addresses also a twisted vortex bundle terminating at a lateral wall of a container, starting from the elementary case when the bundle reduces to a single vortex. The theory considers the laminar regime of the vortex-bundle evolution and investigates the Glaberson-Johnson-Ostermeier instability of the laminar regime, which is a precursor for the transition to the turbulent regime at strong twist of the bundle. The propagation and the rotation velocities of the vortex front (the segment of the vortex bundle diverging to the wall) can be found from the equations of balance for the linear and the angular momenta and the energy. It is demonstrated that the vortex front can move with finite velocity even in the absence of mutual friction (the T=0 limit). The theory is compared with experimental results on vortex-front propagation in superfluid 3He-B. © 2012 American Physical Society.

Mejia-Gomez J.,Hebrew University of Jerusalem
The Israel Medical Association journal : IMAJ | Year: 2012

For the past 15 years gynecological oncologists have been seeking ways to preserve woman's fertility when treating invasive cervical cancer. For some women with small localized invasive cervical cancers, there is now hope for pregnancy after treatment. Many cases of cervical cancer are diagnosed in young woman who wish to preserve their fertility. As more women are delaying childbearing, fertility preservation has become an important consideration. The standard surgical treatment for stage IA2-IB1 cervical cancer is a radical hysterectomy and bilateral pelvic lymphadenectomy. This surgery includes removal of the uterus and cervix, radical resection of the parametrial tissue and upper vagina, and complete pelvic lymphadenectomy. Obviously, the standard treatment does not allow future childbearing. Radical trachelectomy is a fertility-sparing surgical approach developed in France in 1994 by Dr. Daniel Dargent for the treatment of early invasive cervical cancer. Young women wishing to bear children in the future may be candidates for fertility-preservation options. The radical trachelectomy operation has been described and performed abdominally, assisted vaginally by laparoscopy and robotically. In this review we discuss the selection criteria for radical trachelectomy, the various possible techniques for the operation, the oncological and obstetric outcomes, and common complications.

Cai J.,University of Ulm | Retzker A.,University of Ulm | Retzker A.,Hebrew University of Jerusalem | Jelezko F.,University of Ulm | Plenio M.B.,University of Ulm
Nature Physics | Year: 2013

Strongly correlated quantum many-body systems may exhibit exotic phases, such as spin liquids and supersolids. Although their numerical simulation becomes intractable for as few as 50 particles, quantum simulators offer a route to overcome this computational barrier. However, proposed realizations either require stringent conditions such as low temperature/ultra-high vacuum, or are extremely hard to scale. Here, we propose a new solid-state architecture for a scalable quantum simulator that consists of strongly interacting nuclear spins attached to the diamond surface. Initialization, control and read-out of this quantum simulator can be accomplished with nitrogen-vacancy centers implanted in diamond. The system can be engineered to simulate a wide variety of strongly correlated spin models. Owing to the superior coherence time of nuclear spins and nitrogen-vacancy centers in diamond, our proposal offers new opportunities towards large-scale quantum simulation at ambient conditions of temperature and pressure. © 2013 Macmillan Publishers Limited. All rights reserved.

Kidron G.J.,Hebrew University of Jerusalem
Earth Surface Processes and Landforms | Year: 2011

Data concerning runoff and sediment yield in arid zones is of prime importance for hydrologists, geomorphologists, pedologists, ecologists and landscape engineers. For data comparison and extrapolations, runoff and sediment yield are often presented in mass per unit area. Runoff and sediment yield collected on dune slopes over a wide range of plot sizes during 1990-1994 in the Negev Desert, Israel, showed that the contributing area was mainly confined to a narrow belt at the bottom of the slopes. It was therefore hypothesized that the very short rain bursts, capable of runoff generation, may result in a scale effect (SE). Indeed, average duration of duration of consecutive medium and high rain intensities which are potentially above the surface infiltration rate ranged between 2.2 and 3.0 minutes, implying that flow connectivity is largely limited. Based on the intermittent character of the rain spells capable of runoff generation it is argued that SE is an inherent outcome of the rain properties. Yet, it is further argued that the magnitude of the SE is surface-dependent. As a result, it is argued that the conventional way for runoff and sediment yield presentation as mass per unit area implies theoretical misconceptions and may cause gross overestimation in extrapolation and the presentation of runoff and sediment yield in mass per unit width of the slope is suggested. The accuracy of the two extrapolation methods are compared to the actual runoff and sediment yield collected in the field. The data show that extrapolation based on runoff (or sediment) yield per plot width deviates from the actual amounts collected by a factor of 1·1 to 1·3 only while deviating by a factor of 4·2 to 5·6 and 10·7 to 11·8 if the extrapolation is based on large and small plots, respectively. Theoretical and practical reasons for presentation of runoff and sediment yield as mass per unit width are discussed. © 2011 John Wiley & Sons, Ltd.

Marcus Y.,Hebrew University of Jerusalem
Journal of Chemical Thermodynamics | Year: 2013

Values of the adiabatic and isothermal compressibility, κS and κT, of some 80 molten salts at the corresponding temperature of T = 1.1Tm (Tm is the melting point) are obtained from literature data either directly or re-calculated here. For some of the series of salts: alkali metal halides and nitrates, divalent metal halides, and alkali metal sulfates and carbonates the κT values are inversely proportional to the corresponding cohesive energy densities ced (internal energies per unit volume, separately for each class of compounds). The ced values for 1:2 and 2:1 salts not previously evaluated are presented here too. © 2013 Elsevier Ltd. All rights reserved.

Emmanuel S.,Hebrew University of Jerusalem
Chemical Geology | Year: 2014

Water-rock interactions often involve the dissolution of a primary mineral and the precipitation of a new secondary phase. Many of the mechanisms governing such coupled reactions can only be observed directly using high resolution imaging techniques. In this study, atomic force microscopy was used to examine dolostone dissolution at the nanometer and micron scale at different pH conditions in the range 3.5-4.5. During the experiments, a secondary Mg-rich phase comprising nano-scale particles forms on the surface. Importantly, the precipitate does not significantly inhibit dissolution of the dolostone, and although the overall rates of surface retreat are highly dependent on pH, similar mechanisms are found to govern the evolution of the surface. At all pH values, high dissolution rates are observed at etch pits and along grain boundaries, resulting in rate spectra (probability density functions of reaction rates) that are often highly asymmetric and skewed towards higher values. A model based on extreme value theory performs well at capturing the long tails characteristic of the asymmetric distributions, indicating a possible route towards predicting rate spectra in dissolving rocks. © 2013 Elsevier B.V.

Tshori S.,Hebrew University of Jerusalem
Topics in current chemistry | Year: 2014

In this chapter we describe aminoacyl-tRNA synthetase (aaRS) production of dinucleotide polyphosphate in response to stimuli, their interaction with various signaling pathways, and the role of diadenosine tetraphosphate and diadenosine triphosphate as second messengers. The primary role of aaRS is to mediate aminoacylation of cognate tRNAs, thereby providing a central role for the decoding of genetic code during protein translation. However, recent studies suggest that during evolution, "moonlighting" or non-canonical roles were acquired through incorporation of additional domains, leading to regulation by aaRSs of a spectrum of important biological processes, including cell cycle control, tissue differentiation, cellular chemotaxis, and inflammation. In addition to aminoacylation of tRNA, most aaRSs can also produce dinucleotide polyphosphates in a variety of physiological conditions. The dinucleotide polyphosphates produced by aaRS are biologically active both extra- and intra-cellularly, and seem to function as important signaling molecules. Recent findings established the role of dinucleotide polyphosphates as second messengers.

Sonin E.B.,Hebrew University of Jerusalem
Physical Review B - Condensed Matter and Materials Physics | Year: 2012

This article considers the implications of tilt symmetry (symmetry with respect to tilting of the coordinate axis with respect to which vortex motion is studied) in the nonlinear dynamics of Kelvin waves. The conclusion is that although the spectrum of a Kelvin wave is not tilt-invariant, this does not compromise the tilt invariance of the Kelvin-wave cascade that is currently being vigorously debated in the theory of superfluid turbulence. The article investigates the effect of strong kelvon interaction on the power-law exponent for the Kelvin-wave cascade and suggests a simple picture of the crossover from the classical Kolmogorov cascade to the quantum Kelvin-wave cascade, which does not encounter a mismatch of the energy distributions at the crossover and does not require a broad intermediate interval for realization of the crossover. © 2012 American Physical Society.

Baer R.,Hebrew University of Jerusalem
Physical Review Letters | Year: 2010

In Kohn-Sham density functional theory (KS DFT) a fictitious system of noninteracting particles is constructed having the same ground-state (GS) density as the physical system of interest. A fundamental open question in DFT concerns the ability of an exact KS calculation to spot and characterize the GS degeneracies in the physical system. In this Letter we provide theoretical evidence suggesting that the GS density, as a function of position on a 2D manifold of parameters affecting the external potential, is "topologically scarred" in a distinct way by degeneracies. These scars are sufficiently detailed to enable determination of the positions of degeneracies and even the associated Berry phases. We conclude that an exact KS calculation can spot and characterize the degeneracies of the physical system. © 2010 The American Physical Society.

Weinstock M.,Hebrew University of Jerusalem
Israel Journal of Psychiatry and Related Sciences | Year: 2010

Although the etiology of major depressive disorder (MDD) is unknown, it is precipitated in susceptible individuals by adverse events. This review examines the role of intrauterine factors resulting from exposure to stress hormones in the increased vulnerability of the organism to MDD. Severe maternal stress or alcohol intake during the second and third trimesters causes excess release of corticotropin releasing hormone (CRH) and cortisol. These hormones reduce birth weight; impair the feedback regulation of the hypothalamic pituitary adrenal axis (HPA) axis and 5-HT1A and 5-HT2A signaling in key brain areas. Similar changes are seen in patients with MDD and in experimental animals after chronic inescapable stress, prenatal stress or alcohol, which also induce depressive-like behavior in rats, alterations in sleep and circadian rhythms reminiscent of those in humans with MDD. Clinical improvement of MDD by antidepressants is accompanied by normalization of the regulation of the HPA axis and of serotoninergic transmission.

Wiesel A.,Hebrew University of Jerusalem
IEEE Transactions on Signal Processing | Year: 2012

We consider regularized covariance estimation in scaled Gaussian settings, e.g., elliptical distributions, compound-Gaussian processes and spherically invariant random vectors. Asymptotically in the number of samples, the classical maximum likelihood (ML) estimate is optimal under different criteria and can be efficiently computed even though the optimization is nonconvex. We propose a unified framework for regularizing this estimate in order to improve its finite sample performance. Our approach is based on the discovery of hidden convexity within the ML objective. We begin by restricting the attention to diagonal covariance matrices. Using a simple change of variables, we transform the problem into a convex optimization that can be efficiently solved. We then extend this idea to nondiagonal matrices using convexity on the manifold of positive definite matrices. We regularize the problem using appropriately convex penalties. These allow for shrinkage towards the identity matrix, shrinkage towards a diagonal matrix, shrinkage towards a given positive definite matrix, and regularization of the condition number. We demonstrate the advantages of these estimators using numerical simulations. © 2006 IEEE.

Goshen I.,Hebrew University of Jerusalem
Trends in neurosciences | Year: 2014

Over the past 5 years, the incorporation of optogenetics into the study of memory has resulted in a tremendous leap in this field, initiating a revolution in our understanding of the networks underlying cognitive processes. This review will present recent breakthroughs in which optogenetics was applied to illuminate, both literally and figuratively, memory research, and describe the technical approach, together with the opportunities it offers. Specifically, a large body of literature has been generated, setting the foundation for deciphering the spatiotemporal organization of hippocampal-based memory processing and its underlying mechanisms, as well as the contribution of cortical and amygdalar regions to cognition. Copyright © 2014 Elsevier Ltd. All rights reserved.

Metanis N.,Hebrew University of Jerusalem | Hilvert D.,ETH Zurich
Current opinion in chemical biology | Year: 2014

Once considered highly toxic, the element selenium is now recognized as a micronutrient essential for human health. It is inserted co-translationally into many proteins as the non-canonical amino acid selenocysteine, providing the resulting selenoprotein molecules with a range of valuable redox properties; selenocysteine is also increasingly exploited as a structural and mechanistic probe in synthetic peptides and proteins. Here we review topical investigations into the preparation and characterization of natural and artificial selenoproteins. Such molecules are uniquely suited as tools for protein chemistry and as a test bed for studying novel catalytic activities. Copyright © 2014 Elsevier Ltd. All rights reserved.

Rosenfeld D.,Hebrew University of Jerusalem | Bell T.L.,NASA
Journal of Geophysical Research: Atmospheres | Year: 2011

This study shows for the first time statistical evidence that when anthropogenic aerosols over the eastern United States during summertime are at their weekly mid-week peak, tornado and hailstorm activity there is also near its weekly maximum. The weekly cycle in summertime storm activity for 1995-2009 was found to be statistically significant and unlikely to be due to natural variability. It correlates well with previously observed weekly cycles of other measures of storm activity. The pattern of variability supports the hypothesis that air pollution aerosols invigorate deep convective clouds in a moist, unstable atmosphere, to the extent of inducing production of large hailstones and tornados. This is caused by the effect of aerosols on cloud drop nucleation, making cloud drops smaller and hydrometeors larger. According to simulations, the larger ice hydrometeors contribute to more hail. The reduced evaporation from the larger hydrometeors produces weaker cold pools. Simulations have shown that too cold and fast-expanding pools inhibit the formation of tornados. The statistical observations suggest that this might be the mechanism by which the weekly modulation in pollution aerosols is causing the weekly cycle in severe convective storms during summer over the eastern United States. Although we focus here on the role of aerosols, they are not a primary atmospheric driver of tornados and hailstorms but rather modulate them in certain conditions. Copyright 2011 by the American Geophysical Union.

Ovadyahu Z.,Hebrew University of Jerusalem
Physical Review Letters | Year: 2012

We report on measurements of absorption from applied ac fields in Anderson-localized indium-oxide films. The absorption shows a roll-off at a frequency that is much smaller than the electron-electron scattering rate measured at the same temperature in diffusive samples of this material. These results are interpreted as evidence for discreteness of the energy spectrum. © 2012 American Physical Society.

Goldschmidt E.E.,Hebrew University of Jerusalem
Economic Botany | Year: 2013

The Evolution of Fruit Tree Productivity: A Review. Domestication of fruit trees has received far less attention than that of annual crop plants. In particular, very little is known about the evolution of fruit tree productivity. In the wild, most tree species reach reproductive maturity after a long period of juvenility and even then, sexual reproduction appears sporadically, often in a mode of masting. Environmental constraints limit trees' reproductive activity in their natural, wild habitats, resulting in poor, irregular productivity. Early fructification and regular, high rates of productivity have been selected by people, unconsciously and consciously. The reviewed evidence indicates an evolutionary continuum of productivity patterns among trees of wild habitats, intermediary domesticates, and the most advanced domesticates. Alternate bearing appears to represent an intermediate step in the fruit tree evolutionary pathway. The existence of a molecular, genetic mechanism that controls trees' sexual reproduction and fruiting pattern is suggested. © 2013 The Author(s).

Van Rijn J.,Hebrew University of Jerusalem
Aquacultural Engineering | Year: 2013

Recirculating aquaculture systems (RAS) are operated as outdoor or indoor systems. Due to the intensive mode of fish production in many of these systems, waste treatment within the recirculating loop as well as in the effluents of these systems is of primary concern. In outdoor RAS, such treatment is often achieved within the recirculating loop. In these systems, extractive organisms, such as phototrophic organisms and detritivores, are cultured in relatively large treatment compartments whereby a considerable part of the waste produced by the primary organisms is converted in biomass. In indoor systems, capture of solid waste and conversion of ammonia to nitrate by nitrification are usually the main treatment steps within the recirculating loop. Waste reduction (as opposed to capture and conversion) is accomplished in some freshwater and marine indoor RAS by incorporation of denitrification and sludge digestion. In many RAS, whether operated as indoor or outdoor systems, effluent is treated before final discharge. Such effluent treatment may comprise devices for sludge thickening, sludge digestion as well as those for inorganic phosphate and nitrogen removal. Whereas waste disposed from freshwater RAS may be treated in regional waste treatment facilities or may be used for agricultural purposes in the form of fertilizer or compost, treatment options for waste disposed from marine RAS are more limited. In the present review, estimations of waste production as well as methods for waste reduction in the recirculating loop and effluents of freshwater and marine RAS are presented. Emphasis is placed on those processes leading to waste reduction rather than those used for waste capture and conversion. © 2012 Elsevier B.V.

Peer E.,Hebrew University of Jerusalem
Transportation Research Part F: Traffic Psychology and Behaviour | Year: 2011

When drivers are asked to estimate how much time can be saved by increasing speed, they generally underestimate the time saved when increasing from a relatively low speed and overestimate the time saved when increasing from a relatively high speed. This time-saving bias has been demonstrated to affect drivers' estimations of driving speed as well as drivers' personal choice of speed. Specifically, drivers with a high time-saving bias chose unduly high speeds, which sometimes results in speeding, more frequently than drivers with a lower degree of the bias. This study sought to determine whether this relationship would be mediated by individual differences in driving behavior - including drivers' attitudes, norms and habits regarding speeding behavior as well as their level of aberrant driving behavior (committing aggressive or ordinary violations, errors or lapses in driving, measured by the Driver Behaviour Questionnaire). The results showed that the time-saving bias predicted estimations of required speed better than any of these factors, and also better than drivers' age, gender, education and income, as well as the number of years they have had a license and their monthly driving kilometrage, their prior speeding violations and crash involvement. In predicting drivers' personal speed choices, the time-saving bias was second only to the frequency of committing ordinary violations. © 2011 Elsevier Ltd. All rights reserved.

Cohen E.,Hebrew University of Jerusalem
Advances in Insect Physiology | Year: 2013

Insects, which are characterized by a comparative large surface area versus a relative small size, are generally challenged by osmotic stresses and, in particular, when exposed to hot, dry, salty and freezing environments. Furthermore, insects feeding on large volumes of fluids such as blood, phloem-sap or nectar confront a different type of osmotic challenges. The digestive tract and associated Malpighian tubules are the major organs active in alleviating such challenges. Various passive and active transepithelial transport facilitators, such as pumps, ion exchangers, co-transporters and ion and water channels (aquaporins), are under the hormonal control by biogenic amines and various neuropeptides. Interaction of the neurohormones with their respective receptors induces cascade pathways that trigger diuretic or antidiuretic responses. Since water homeostasis and osmoregulation are crucial for the survival of insects, the elaborate physiological mechanisms that have evolved in maintaining balance of water and electrolytes are potential targets for interference. Synthesis of metabolically and environmentally biostable neuropeptidergic analogs in combination with receptor assay-guided structure-activity studies could be instrumental in discovering highly potent molecular leads that are vital in generating efficient and selective insect control agents. © 2013 Elsevier Ltd.

Nesher G.,Shaare Zedek Medical Center | Nesher G.,Hebrew University of Jerusalem
Journal of Autoimmunity | Year: 2014

Giant-cell arteritis (GCA) involves the major branches of the aorta with predilection for the extracranial branches of the carotid artery. It occurs in individuals older than 50 years and the incidence increases with age. The signs and symptoms of giant cell arteritis can be classified into four subsets: cranial arteritis, extracranial arteritis, systemic symptoms and polymyalgia rheumatica. Patients may develop any combination of these manifestations, associated with laboratory evidence of an acute-phase reaction. The only test that confirms GCA diagnosis is a temporal artery biopsy, showing vasculitis with mononuclear cell inflammatory infiltrates, often with giant cells. Due to the focal and segmental nature of the infiltrates, areas of inflammation may be missed by the biopsy and the histological examination is normal in about 15% of the cases. Some imaging modalities may aid in the diagnosis of GCA. Among those, color duplex ultrasonography of the temporal arteries is more commonly used. There are no independent validating criteria to determine whether giant cell arteritis is present when a temporal artery biopsy is negative. The American College of Rheumatology criteria for the classification of giant cell arteritis may assist in the diagnosis. However, meeting classification criteria is not equivalent to making the diagnosis in individual patients, and the final diagnosis should be based on all clinical, laboratory, imaging and histological findings. Glucocorticoids are the treatment of choice for GCA. The initial dose is 40-60mg/day for most uncomplicated cases. Addition of low-dose aspirin (100mg/d) has been shown to significantly decrease the rate of vision loss and stroke during the course of the disease. © 2014 Elsevier Ltd.

Amrani A.,Hebrew University of Jerusalem
Annual Review of Earth and Planetary Sciences | Year: 2014

Organosulfur compounds (OSCs) play important roles in the formation, preservation, and thermal degradation of sedimentary organic matter and the associated petroleum generation. Improved analytical techniques for S isotope analysis have recently enhanced our understanding of the mechanisms for OSC formation and maturation and their associated S isotope distributions. The close interaction of OSCs with inorganic S species throughout their formation and maturation affects their 34S/32S isotopic ratio (δ34S), forming specific signatures for distinct sources and processes. Ultimately, thermal maturation homogenizes the δ34S values of different fractions and individual compounds. Reservoir processes such as thermochemical sulfate reduction (TSR) introduce exogenous and isotopically distinct S into hydrocarbons and can significantly change the δ34S of petroleum or kerogen. Specific OSCs react at different rates and thus can be used to evaluate the extent of processes such as TSR. This article reviews factors that affect the 34S/32S isotopic distribution of OSCs along pathways of formation, diagenesis, and thermal alteration. © 2014 by Annual Reviews. All rights reserved.

Dekel A.,Hebrew University of Jerusalem | Burkert A.,Universitaets Sternwarte Scheinerstr 1 | Burkert A.,Max Planck Institute for Physics
Monthly Notices of the Royal Astronomical Society | Year: 2014

We study the origin of high-redshift, compact, quenched spheroids (red nuggets) through the dissipative shrinkage of gaseous discs into compact star-forming systems (blue nuggets). The discs, fed by cold streams, undergo violent disc instability that drives gas into the centre (along with mergers). The inflow is dissipative when its time-scale is shorter than the star formation time-scale. This implies a threshold of ~0.28 in the cold-to-total mass ratio within the disc radius. For the typical gas fraction ~0.5 at z ~ 2, this threshold is traced back to a maximum spin parameter of ~0.05, implying that ~half the star-forming galaxies contract to blue nuggets, while the rest form extended stellar discs. Thus, the surface density of blue galaxies is expected to be bimodal about ~109M⊙ kpc-2, slightly increasing with mass. The blue nuggets are expected to be rare at low z when the gas fraction is low. The blue nuggets quench to red nuggets by complementary internal and external mechanisms. Internal quenching by a compact bulge, in a fast mode and especially at high z, may involve starbursts, stellar and active galactic nucleus feedback, or Q-quenching. Quenching due to hot-medium haloes above 1012M⊙ provides maintenance and a slower mode at low redshift. These predictions are confirmed in simulations and are consistent with observations at z = 0-3. © 2013 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.

Argov Z.,Hebrew University of Jerusalem
European Journal of Neurology | Year: 2015

Statins intolerance is mainly due to their side effects on the neuromuscular system (primarily muscle). It has become an important issue because of the major cardiovascular risk reduction of this class of drugs. However, the facts related to these side effects are sometimes under-recognized or controversial. A literature review of the recent developments in the field is given. The clinical definition of statin myopathy and its presentation are not suitable for the myology field. Management and prevention are not validated. More genetic risk factors need to be established. Neurologists should become more involved in statin intolerance evaluation and management. © 2014 EAN.

Bettelheim E.,Hebrew University of Jerusalem | Glazman L.,Yale University
Physical Review Letters | Year: 2012

The evolution of an initially smooth spatial inhomogeneity in the density of a one-dimensional Fermi gas is well described by classical mechanics. The classical evolution leads to the formation of a shock wave: the density develops kinks in its coordinate dependence. We show that quantum corrections to the shock wave produce density ripples which run off the kinks. Despite their quantum origin, the amplitude and period of the ripples are expressed only in terms of classical objects derived from a smooth density profile. © 2012 American Physical Society.

Bekenstei J.D.,Hebrew University of Jerusalem
Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences | Year: 2011

The impressive success of the standard cosmological model has suggested to many that its ingredients are all that one needs to explain galaxies and their systems. I summarize a number of known problems with this programme. They might signal the failure of standard gravity theory on galaxy scales. The requisite hints as to the alternative gravity theory may lie with the modified Newtonian dynamics (MOND) paradigm, which has proved to be an effective summary of galaxy phenomenology. A simple nonlinear modified gravity theory does justice to MOND at the non-relativistic level, but cannot be consistently promoted to relativistic status. The obstacles were first side-stepped with the formulation of tensor-vector-scalar theory (TeVe S), a covariant-modified gravity theory. I review its structure, its MOND and Newtonian limits, and its performance in the face of galaxy phenomenology. I also summarize features of TeVe S cosmology and describe the confrontation with data from strong and weak gravitational lensing. © 2011 The Royal Society.

Harrus S.,Hebrew University of Jerusalem | Waner T.,Israel Institute for Biological Research
Veterinary Journal | Year: 2011

Canine monocytotropic ehrlichiosis (CME), caused by the rickettsia Ehrlichia canis, an important canine disease with a worldwide distribution. Diagnosis of the disease can be challenging due to its different phases and multiple clinical manifestations. CME should be suspected when a compatible history (living in or traveling to an endemic region, previous tick exposure), typical clinical signs and characteristic hematological and biochemical abnormalities are present. Traditional diagnostic techniques including hematology, cytology, serology and isolation are valuable diagnostic tools for CME, however a definitive diagnosis of E. canis infection requires molecular techniques. This article reviews the current literature covering the diagnosis of infection caused by E. canis. © 2010 Elsevier Ltd.

Avnir D.,Hebrew University of Jerusalem
Accounts of Chemical Research | Year: 2014

The many millions of organic, inorganic, and bioorganic molecules represent a very rich library of chemical, biological, and physical properties that do not show up among the approximately 100 metals. The ability to imbue metals with any of these molecular properties would open up tremendous potential for the development of new materials. In addition to their traditional features and their traditional applications, metals would have new traits, which would merge their classical virtues such as conductivity and catalytic activity with the diverse properties of these molecules.In this Account, we describe a new materials methodology, which enables, for the first time, the incorporation and entrapment of small organic molecules, polymers, and biomolecules within metals. These new materials are denoted dopant@metal. The creation of dopant@metal yields new properties that are more than or different from the sum of the individual properties of the two components. So far we have developed methods for the doping of silver, copper, gold, iron, palladium, platinum, and some of their alloys, as well as Hg-Ag amalgams. We have successfully altered classical metal properties (such as conductivity), induced unorthodox properties (such as rendering a metal acidic or basic), used metals as heterogeneous matrices for homogeneous catalysts, and formed new metallic catalysts such as metals doped with organometallic complexes. In addition, we have created materials that straddle the border between polymers and metals, we have entrapped enzymes to form bioactive metals, we have induced chirality within metals, we have made corrosion-resistant iron, we formed efficient biocidal materials, and we demonstrated a new concept for batteries.We have developed a variety of methods for synthesizing dopant@metals including aqueous homogeneous and heterogeneous reductions of the metal cations, reductions in DMF, electrochemical entrapments, thermal decompositions of zerovalent metal carbonyls, and dissolution during amalgam formation. The structures of these dopant@metal materials indicate that metals entrap the organic molecules within their agglomerated nanocrystals. As a result, these materials are porous, making the dopant accessible for chemical reactions, in particular for catalysis. We have prepared these materials in a variety of forms, including powder, granules, pressed discs, thin films, thick films, sub-micrometer particles, and nanometric particles decorating ceramic nanofibers.Entrapment and adsorption are very different processes. If entrapped, water-soluble molecules cannot be extracted, but the same molecules, if adsorbed, are easily washed away. Likewise, most of the special properties that we have observed, such as major improvements or changes in catalytic activity, completely different thermal gravimetric analysis behavior, and more, are observed only in the entrapped cases. © 2013 American Chemical Society.

Marcus Y.,Hebrew University of Jerusalem
Journal of Physical Chemistry B | Year: 2014

Isothermal compressibility data of 23 aqueous electrolyte solutions at 25 °C from the literature are used to calculate their hydration numbers, which diminish as the concentration increases. Their limit at very high concentration is near the "number of adsorption sites" of water molecules on the ions, obtained by the BET method. On the contrary, hydration numbers obtained from ultrasound speed measurements yielding isentropic compressibilities cannot be valid, being much too large at infinite dilution. © 2014 American Chemical Society.

Shaulian E.,Hebrew University of Jerusalem
Cellular Signalling | Year: 2010

Since its discovery more than two decades ago the involvement of the Activating protein 1 (AP-1) in proliferation, inflammation, differentiation, apoptosis, cellular migration and wound healing has been intensively studied. A model based on the early studies suggested antagonistic roles for the Jun proteins in proliferation and transformation. c-Jun was suggested to enhance transformation whereas JunB suggested to inhibit it in an antagonistic manner. Surprisingly, despite accumulation of data obtained from animal models regarding the role of Jun proteins in cancer and identification of oncogenic pathways regulating them, their involvement in human cancer was not demonstrated until recently. Here, we will describe the current knowledge about the roles of Jun proteins in human neoplasia. We will focus on the pathological examples demonstrating that the initial dogma has to be reexamined. For example, like c-Jun, JunB seems to play an oncogenic role in lymphomas, particularly in Hodgkin's lympomas. Furthermore, unlike the antagonistic activities of c-Jun and JunB in the transcription of genes coding for major cell cycle regulators such as CyclinD or p16INK4A, the transcription of other cell cycle regulating genes is modified similarly by c-Jun or JunB. Interestingly, some of these genes such as the ones coding for CyclinA or p19ARF are important players in either positive or negative regulation of cellular proliferation and survival. Finally, we will also discuss results posing JNK, known so far as the major activator of c-Jun, as a negative regulator of c-Jun level and activity. These recent findings suggest that the role of each Jun protein in neoplasia as well as in cellular survival should be examined in a context-dependent manner. © 2010 Elsevier Inc.

Marcus Y.,Hebrew University of Jerusalem
Journal of Chemical and Engineering Data | Year: 2013

The densities ρ of molten salt hydrates CpA q·nH2O were obtained from the literature over a range of temperatures. The values of ρ and the pertinent isothermal expansibilities αP and molar volumes at the corresponding temperature of 1.1 times the melting point (Tm/K) are tabulated. The molar volumes of the melts are discussed in terms of the electrostriction of the water. © 2013 American Chemical Society.

Braslavsky I.,Hebrew University of Jerusalem
Journal of visualized experiments : JoVE | Year: 2013

Ice-binding proteins (IBPs), including antifreeze proteins, ice structuring proteins, thermal hysteresis proteins, and ice recrystallization inhibition proteins, are found in cold-adapted organisms and protect them from freeze injuries by interacting with ice crystals. IBPs are found in a variety of organism, including fish(1), plants(2, 3), arthropods(4, 5), fungi(6), and bacteria(7). IBPs adsorb to the surfaces of ice crystals and prevent water molecules from joining the ice lattice at the IBP adsorption location. Ice that grows on the crystal surface between the adsorbed IBPs develops a high curvature that lowers the temperature at which the ice crystals grow, a phenomenon referred to as the Gibbs-Thomson effect. This depression creates a gap (thermal hysteresis, TH) between the melting point and the nonequilibrium freezing point, within which ice growth is arrested(8-10), see Figure 1. One of the main tools used in IBP research is the nanoliter osmometer, which facilitates measurements of the TH activities of IBP solutions. Nanoliter osmometers, such as the Clifton instrument (Clifton Technical Physics, Hartford, NY,) and Otago instrument (Otago Osmometers, Dunedin, New Zealand), were designed to measure the osmolarity of a solution by measuring the melting point depression of droplets with nanoliter volumes. These devices were used to measure the osmolarities of biological samples, such as tears(11), and were found to be useful in IBP research. Manual control over these nanoliter osmometers limited the experimental possibilities. Temperature rate changes could not be controlled reliably, the temperature range of the Clifton instrument was limited to 4,000 mOsmol (about -7.5 °C), and temperature recordings as a function of time were not an available option for these instruments. We designed a custom-made computer-controlled nanoliter osmometer system using a LabVIEW platform (National Instruments). The cold stage, described previously(9, 10), contains a metal block through which water circulates, thereby functioning as a heat sink, see Figure 2. Attached to this block are thermoelectric coolers that may be driven using a commercial temperature controller that can be controlled via LabVIEW modules, see Figure 3. Further details are provided below. The major advantage of this system is its sensitive temperature control, see Figure 4. Automated temperature control permits the coordination of a fixed temperature ramp with a video microscopy output containing additional experimental details. To study the time dependence of the TH activity, we tested a 58 kDa hyperactive IBP from the Antarctic bacterium Marinomonas primoryensis (MpIBP)(12). This protein was tagged with enhanced green fluorescence proteins (eGFP) in a construct developed by Peter Davies' group (Queens University)(10). We showed that the temperature change profile affected the TH activity. Excellent control over the temperature profile in these experiments significantly improved the TH measurements. The nanoliter osmometer additionally allowed us to test the recrystallization inhibition of IBPs(5, 13). In general, recrystallization is a phenomenon in which large crystals grow larger at the expense of small crystals. IBPs efficiently inhibit recrystallization, even at low concentrations(14, 15). We used our LabVIEW-controlled osmometer to quantitatively follow the recrystallization of ice and to enforce a constant ice fraction using simultaneous real-time video analysis of the images and temperature feedback from the sample chamber(13). The real-time calculations offer additional control options during an experimental procedure. A stage for an inverted microscope was developed to accommodate temperature-controlled microfluidic devices, which will be described elsewhere(16). The Cold Stage System The cold stage assembly (Figure 2) consists of a set of thermoelectric coolers that cool a copper plate. Heat is removed from the stage by flowing cold water through a closed compartment under the thermoelectric coolers. A 4 mm diameter hole in the middle of the copper plate serves as a viewing window. A 1 mm diameter in-plane hole was drilled to fit the thermistor. A custom-made copper disc (7 mm in diameter) with several holes (500 μm in diameter) was placed on the copper plate and aligned with the viewing window. Air was pumped at a flow rate of 35 ml/sec and dried using Drierite (W.A. Hammond). The dry air was used to ensure a dry environment at the cooling stage. The stage was connected via a 9 pin connection outlet to a temperature controller (Model 3040 or 3150, Newport Corporation, Irvine, California, US). The temperature controller was connected via a cable to a computer GPIB-PCI card (National instruments, Austin, Texas, USA).

Harfouche A.,University of Tuscia | Meilan R.,Purdue University | Altmane A.,Hebrew University of Jerusalem
Trends in Biotechnology | Year: 2011

Forest trees provide raw materials, help to maintain biodiversity and mitigate the effects of climate change. Certain tree species can also be used as feedstocks for bioenergy production. Achieving these goals may require the introduction or modified expression of genes to enhance biomass production in a sustainable and environmentally responsible manner. Tree genetic engineering has advanced to the point at which genes for desirable traits can now be introduced and expressed efficiently; examples include biotic and abiotic stress tolerance, improved wood properties, root formation and phytoremediation. Transgene confinement, including flowering control, may be needed to avoid ecological risks and satisfy regulatory requirements. This and stable expression are key issues that need to be resolved before transgenic trees can be used commercially. © 2010 Elsevier Ltd.

Salah Z.,Hebrew University of Jerusalem
Cell death & disease | Year: 2013

The WWOX tumor suppressor is a WW domain-containing protein. Its function in the cell has been shown to be mediated, in part, by interacting with its partners through its first WW (WW1) domain. Here, we demonstrated that WWOX via WW1 domain interacts with p53 homolog, ΔNp63α. This protein-protein interaction stabilizes ΔNp63α, through antagonizing function of the E3 ubiquitin ligase ITCH, inhibits nuclear translocation of ΔNp63α into the nucleus and suppresses ΔNp63α transactivation function. Additionally, we found that this functional crosstalk reverses cancer cells resistance to cisplatin, mediated by ΔNp63α, and consequently renders these cells more sensitive to undergo apoptosis. These findings suggest a functional crosstalk between WWOX and ΔNp63α in tumorigenesis.

Hirsch H.J.,Hebrew University of Jerusalem
Hormone Research in Paediatrics | Year: 2014

Background: Minipuberty describes transient activation of the hypothalamic-pituitary-gonadal axis occurring during the first few months of life. Hormone levels during minipuberty were described in only a few Prader-Willi syndrome (PWS) infant boys and have not been reported in PWS infant girls. Objectives: To measure gonadotropins and gonadal hormones in PWS male and female infants and assess gender-specific patterns of hormone secretion. Methods: Hormone levels in 14 (9 male, 5 female) PWS infants ages 1-3 months were compared with reference ranges for normal infants and in 44 prepubertal PWS children (27 female, 17 male). Results: Compared to prepubertal boys, hormone levels (median and range) for PWS infant boys were increased: LH 2.8 mIU/ml (1.2-6.2), FSH 4.4 mIU/ml (1.0-19.5), testosterone 4.0 nmol/l (3.0-7.0), inhibin B 219 pg/ml (141-325), and AMH 79 ng/ml (45-157). Hormone levels in infant girls were not significantly different from levels in prepubertal girls. LH, inhibin B, and AMH were higher in male infants than in female infants. LH/FSH ratios were 0.56 (0.24-1.77) in boys versus 0.09 (0.04-0.17) in girls (p = 0.003). Conclusions: Hormone levels in PWS infant boys are in the expected minipuberty range. By contrast, reproductive hormones in most PWS infant girls did not differ from levels in prepubertal girls. © 2014 S. Karger AG, Basel.

Froy O.,Hebrew University of Jerusalem
Endocrine Reviews | Year: 2010

Obesity has become a serious public health problem and a major risk factor for the development of illnesses, such as insulin resistance and hypertension. Human homeostatic systems have adapted to daily changes in light and dark in a way that the body anticipates the sleep and activity periods. Mammals have developed an endogenous circadian clock located in the suprachiasmatic nuclei of the anterior hypothalamus that responds to the environmental light-dark cycle. Similar clocks have been found in peripheral tissues, such as the liver, intestine, and adipose tissue, regulating cellular and physiological functions. The circadian clock has been reported to regulate metabolism and energy homeostasis in the liver and other peripheral tissues. This is achieved by mediating the expression and/or activity of certain metabolic enzymes and transport systems. In return, key metabolic enzymes and transcription activators interact with and affect the core clock mechanism. In addition, the core clock mechanism has been shown to be linked with lipogenic and adipogenic pathways. Animals with mutations in clock genes that disrupt cellular rhythmicity have provided evidence for the relationship between the circadian clock and metabolic homeostasis. In addition, clinical studies in shift workers and obese patients accentuate the link between the circadian clock and metabolism. This review will focus on the interconnection between the circadian clock and metabolism, with implications for obesity and how the circadian clock is influenced by hormones, nutrients, and timed meals. Copyright © 2010 by The Endocrine Society.

Chipman A.D.,Hebrew University of Jerusalem
BioEssays | Year: 2010

Different sources of data on the evolution of segmentation lead to very different conclusions. Molecular similarities in the developmental pathways generating a segmented body plan tend to suggest a segmented common ancestor for all bilaterally symmetrical animals. Data from paleontology and comparative morphology suggest that this is unlikely. A possible solution to this conundrum is that throughout evolution there was a parallel co-option of gene regulatory networks that had conserved ancestral roles in determining body axes and in elongating the anterior-posterior axis. Inherent properties in some of these networks made them easily recruitable for generating repeated patterns and for determining segmental boundaries. Phyla where this process happened are among the most successful in the animal kingdom, as the modular nature of the segmental body organization allowed them to diverge and radiate into a bewildering array of variations on a common theme. © 2010 Wiley Periodicals, Inc.

Froy O.,Hebrew University of Jerusalem | Miskin R.,Weizmann Institute of Science
Aging | Year: 2010

Increased longevity and improved health can be achieved in mammals by two feeding regimens, caloricrestriction (CR), which limits the amount of daily calorie intake, and intermittent fasting (IF), which allows the food to beavailable ad libitum every other day. The precise mechanisms mediating these beneficial effects are still unresolved.Resetting the circadian clock is another intervention that can lead to increased life span and well being, while clockdisruption is associated with aging and morbidity. Currently, a large body of evidence links circadian rhythms withmetabolism and feeding regimens. In particular, CR, and possibly also IF, can entrain the master clock located in thesuprachiasmatic nuclei (SCN) of the brain hypothalamus. These findings raise the hypothesis that the beneficial effectsexerted by these feeding regimens could be mediated, at least in part, through resetting of the circadian clock, thus leadingto synchrony in metabolism and physiology. This hypothesis is reinforced by a transgenic mouse model showingspontaneously reduced eating alongside robust circadian rhythms and increased life span. This review will summarizerecent findings concerning the relationships between feeding regimens, circadian rhythms, and metabolism withimplications for ageing attenuation and life span extension. © Froy and Miskin.

Bloch G.,Hebrew University of Jerusalem
Journal of Biological Rhythms | Year: 2010

The honeybee has long been an important model for studying the interplay between the circadian clock and complex behaviors. This article reviews studies further implicating the circadian clock in complex social behaviors in bees. The article starts by introducing honeybee social behavior and sociality and then briefly summarizes current findings on the molecular biology and neuroanatomy of the circadian system of honeybees that point to molecular similarities to the mammalian clockwork rather than to that of Drosophila. Foraging is a social behavior in honeybees that relies on the circadian clock for timing visits to flowers, time-compensated sun-compass navigation, and dance communication used by foragers to recruit nestmates to rewarding flower patches. The circadian clock is also important for the social organization of honeybee societies. Social factors influence the ontogeny of circadian rhythms and are important for social synchronization of worker activities. Both queen and worker bees switch between activities with and without circadian rhythms. In workers this remarkable plasticity is associated with the division of labor; nurse bees care for the brood around the clock with similar levels of clock gene expression throughout the day, whereas foragers have strong behavioral circadian rhythms with oscillating brain clock gene levels. This plasticity in circadian rhythms is regulated by direct contact with the brood and is context-specific in that nurse bees that are removed from the hive exhibit activity with strong behavioral and molecular rhythms. These studies on the sociochronobiology of honeybees and comparative studies with other social insects suggest that the evolution of sociality has influenced the characteristics of the circadian system in honeybees. © 2010 Sage Publications.

Froy O.,Hebrew University of Jerusalem
Ageing Research Reviews | Year: 2013

Life span extension has been a goal of research for several decades. Resetting circadian rhythms leads to well being and increased life span, while clock disruption is associated with increased morbidity accelerated aging. Increased longevity and improved health can be achieved by different feeding regimens that reset circadian rhythms and may lead to better synchrony in metabolism and physiology. This review focuses on the circadian aspects of energy metabolism and their relationship with aging in mammals. © 2013 Elsevier B.V.

Haj-Yahia M.M.,Hebrew University of Jerusalem
Aggression and Violent Behavior | Year: 2011

Several models and modalities of intervention with battered women have been developed over the past three decades. The common assumptions underlying these interventions include: violence and abuse are never appropriate in intimate relationships; battered women have a non-negotiable right to safety; the women's strengths and competencies should be emphasized rather than their weaknesses and problems; and battered women should be helped to understand how the social and familial contexts in which they are considered inferior citizens and family members contribute to violence against them. These interventions, as well as the principles and philosophies that underlie them, have been developed and implemented in individualistic, Western, and post-industrial societies. Hence, their suitability for implementation among battered women from collectivist and less developed societies has been called into question. In this article, the conceptual framework proposed by Triandis, Brislin, and Hui (1988) is used as the basis for exploring the characteristics of collectivist societies and their relevance to interventions with battered women. In addition, some issues, controversies, and dilemmas that can arise in those interventions are discussed. The article concludes with an epilogue that provides suggestions for further research on these issues and controversies. © 2011 Elsevier Ltd.

Sade N.,Hebrew University of Jerusalem
Plant signaling & behavior | Year: 2012

Water scarcity is a critical limitation for agricultural systems. Two different water management strategies have evolved in plants: an isohydric strategy and an anisohydric strategy. Isohydric plants maintain a constant midday leaf water potential (Ψleaf) when water is abundant, as well as under drought conditions, by reducing stomatal conductance as necessary to limit transpiration. Anisohydric plants have more variable Ψleaf and keep their stomata open and photosynthetic rates high for longer periods, even in the presence of decreasing leaf water potential. This risk-taking behavior of anisohydric plants might be beneficial when water is abundant, as well as under moderately stressful conditions. However, under conditions of intense drought, this behavior might endanger the plant. We will discuss the advantages and disadvantages of these two water-usage strategies and their effects on the plant's ability to tolerate abiotic and biotic stress. The involvement of plant tonoplast AQPs in this process will also be discussed.

Gruenbaum Y.,Hebrew University of Jerusalem
Annual Review of Biochemistry | Year: 2015

This article discusses three reviews on the theme of nuclear organization. Copyright © 2015 by Annual Reviews. All rights reserved.

Frost R.,Hebrew University of Jerusalem | Frost R.,Haskins Laboratories
Behavioral and Brain Sciences | Year: 2012

In the last decade, reading research has seen a paradigmatic shift. A new wave of computational models of orthographic processing that offer various forms of noisy position or context-sensitive coding have revolutionized the field of visual word recognition. The influx of such models stems mainly from consistent findings, coming mostly from European languages, regarding an apparent insensitivity of skilled readers to letter order. Underlying the current revolution is the theoretical assumption that the insensitivity of readers to letter order reflects the special way in which the human brain encodes the position of letters in printed words. The present article discusses the theoretical shortcomings and misconceptions of this approach to visual word recognition. A systematic review of data obtained from a variety of languages demonstrates that letter-order insensitivity is neither a general property of the cognitive system nor a property of the brain in encoding letters. Rather, it is a variant and idiosyncratic characteristic of some languages, mostly European, reflecting a strategy of optimizing encoding resources, given the specific structure of words. Since the main goal of reading research is to develop theories that describe the fundamental and invariant phenomena of reading across orthographies, an alternative approach to model visual word recognition is offered. The dimensions of a possible universal model of reading, which outlines the common cognitive operations involved in orthographic processing in all writing systems, are discussed. © 2012 Cambridge University Press.

Marcus Y.,Hebrew University of Jerusalem
Journal of Physical Chemistry B | Year: 2012

The standard partial molar volumes, V∞(i,T), of 12 univalent ions (alkali metal, ammonium, halide, nitrate, and perchlorate) and five divalent ions (alkaline earth and sulfate) in water at 125, 150, 175, and 200 °C and at 2 MPa were derived from the data of Ellis. Similar data for NH4 + and NO3 - at 0-100 °C, not included in Part 4, were added, derived from his data too. The (negative) electrostrictive volumes, ΔVelstr(i,T), of these ions at infinite dilution were obtained from the shell-by-shell calculation of the electrostriction according to Marcus and Hefter that takes into account the mutual dependence of the relative permittivity of the water around the ion and the electrical field strength at it. The expanded volumes of the ions, defined as VExpan(i,T) = V∞(i,T) - ΔV elstr(i,T), were then derived and compared with their intrinsic volumes, calculated according to Glueckauf. The calculation yields also the spatial extension of the dielectrically saturated region around the ions. The numbers of water molecules, the molar volume of which is affected by the ions at infinite dilution, were estimated from the ratio of ΔV elstr(i,T) and VWel(T), the latter being the average molar electrostriction of the water in the vicinity of the ions. © 2012 American Chemical Society.

Krolik J.H.,Johns Hopkins University | Piran T.,Hebrew University of Jerusalem
Astrophysical Journal | Year: 2011

We propose that the remarkable object Swift J1644+57, in which multiple recurring hard X-ray flares were seen over a span of several days, is a system in which a white dwarf was tidally disrupted by an intermediate-mass black hole. Disruption of a white dwarf rather than a main-sequence star offers a number of advantages in understanding the multiple, and short, timescales seen in the light curve of this system. In particular, the short internal dynamical timescale of a white dwarf offers a more natural way of understanding the short rise times (100s) observed. The relatively long intervals between flares (5 × 104s) may also be readily understood as the period between successive pericenter passages of the remnant white dwarf. In addition, the expected jet power is larger when a white dwarf is disrupted. If this model is correct, the black hole responsible must have a mass ≲ 105 M ⊙. © 2011. The American Astronomical Society. All rights reserved.

Ovadyahu Z.,Hebrew University of Jerusalem
Physical Review B - Condensed Matter and Materials Physics | Year: 2015

It is demonstrated that persistent photoconductivity (PPC), well studied in lightly-doped semiconductors, is observable in GeSbTe compounds using infrared excitation at cryogenic temperatures. The low levels of energy flux necessary to induce an appreciable effect seems surprising given the high carrier concentration n of these ternary alloys (n>1020cm-3). On the other hand, their high density of carriers makes GeSbTe films favorable candidates for exhibiting intrinsic electron-glass effects with long relaxation times. These are indeed observed in GeSbTe thin films that are Anderson-localized. In particular, a memory dip is observed in samples with sheet resistances larger than ≈105Ω at T≈4 K with similar characteristics as in other systems that exhibit intrinsic electron-glass effects. Persistent photoconductivity, however, is observable in GeSbTe films even for sheet resistances of the order of 103Ω, well below the range of disorder required for observing electron-glass effects. These two nonequilibrium phenomena, PPC and electron glass, are shown to be of different nature in terms of other aspects as well. In particular, their relaxation dynamics is qualitatively different; the excess conductance ΔG associated with PPC decays with time as a stretched exponential whereas a logarithmic relaxation law characterizes ΔG(t) of all electron glasses studied to date. Surprisingly, the magnitude of the memory dip is enhanced when the system is in the PPC state. This counter-intuitive result may be related to the compositional disorder in these materials extending over mesoscopic scales. Evidence in support of this scenario is presented and discussed. © 2015 American Physical Society.

Affected by the interrelationships between the air mass and the substrate properties, dew measurements entail numerous difficulties. Inattentiveness to the complexities involved may result in inconsistent and consequently unreliable data and thus in misleading conclusions. This is especially important in dew deserts such as the Negev where dew may be regarded as an important water source. In an attempt to highlight some of the factors that may affect dew condensation, an experimental approach was adapted during which dew condensation at different surfaces (smooth and ragged Plexiglas, bright limestone and dark flint cobbles), at various size substrata with identical axes (of 2.5, 5, 10, 20, 30 and 40. cm) or different size axes (of 10 × 20, 10 × 30 and 10 × 40. cm), and substrata at different heights and settings was measured. Some of the settings explored were also sheltered by a shrub, a cave, an 80-cm-tall cliff and neighboring cobbles.No significant differences were found in the dew amounts condensing on the limestone and the flint cobbles. Smooth Plexiglas surfaces yielded significantly higher amounts than a ragged Plexiglas surface. As for the substratum height and size, the dew amounts increased with height (from 0.7 to 10.0. cm) and size (from 2.5 × 2.5. cm to 40 × 40. cm). However, an increase in the long axis (a-axis) to 20, 30 and 40. cm while leaving the b-axis constant (at 10. cm) resulted in only a slight increase in the dew amounts in comparison to a 10 × 10. cm substratum. While confined to non-sheltered habitats, dew at partially sheltered habitats (such as the margin of a shrub or a cave, the vicinity of a cliff and on 7-cm-high cobble surrounded by 15-cm-high cobbles) was significantly lower than at the exposed habitats. The differences in dew amounts coincided with minute differences in the surface temperatures, explained as resulting from differences in the outgoing nocturnal longwave radiational cooling. The findings may shed light on the dew regime of lithobionts at different microhabitats and upon inconsistent values reported in the literature. © 2010 Elsevier B.V.

Wilschanski M.,Hebrew University of Jerusalem
Discovery Medicine | Year: 2013

Cystic fibrosis (CF) is the most common lethal monogenic disorder. Life expectancy of CF patients is rising towards a mean of 40 years with advances in all aspects of therapy apart from treating the basic molecular defect. In the twenty three years since the discovery of the gene that causes cystic fibrosis, our knowledge of how mutations in this gene cause the varied pathophysiological manifestations of this disease has increased substantially. This knowledge has led to the possibility of new therapeutic approaches aimed at the basic defect. Apart from gene therapy, several novel compounds have recently been discovered using high-throughput screening which appear promising enough to develop into effective drugs to cure the basic defect. This article will summarize our current knowledge of mutation specific therapy and will focus on orally bioavailable potentiators and correctors and suppressors of premature termination codons. Further development of these drugs will enable treatment of the basic defect in diseases like CF and open the door for treatment of disease according to gene sequencing -- true personalized medicine. © Discovery Medicine.

Berry E.M.,Hebrew University of Jerusalem
Public health nutrition | Year: 2011

To place the Mediterranean diet (MedDi) in the context of the cultural history of the Middle East and emphasise the health effects of some of the biblical seven species - wheat, barley, grapes, figs, pomegranates, olives and date honey. Review of the literature concerning the benefits of these foods. Middle East and Mediterranean Basin. Mediterranean populations and clinical studies utilising the MedDi. The MedDi has been associated with lower rates of CVD, and epidemiological evidence promotes the benefits of consuming fruit and vegetables. Recommended foods for optimal health include whole grain, fish, wine, pomegranates, figs, walnuts and extra virgin olive oil. The biblical traditional diet, including the seven species and additional Mediterranean fruits, has great health advantages, especially for CVD. In addition to the diet, lifestyle adaptation that involves increasing physical activity and organised meals, together with healthy food choices, is consistent with the traditional MedDi. The MedDi is a manageable, lifestyle-friendly diet that, when fortified with its biblical antecedent attributes, may prove to be even more enjoyable and considerably healthier in combating the obesogenic environment and in decreasing the risks of the non-communicable diseases of modern life than conventional, modern dietary recommendations. The biblical seven species, together with other indigenous foods from the Middle East, are now scientifically recognised as healthy foods, and further improve the many beneficial effects of the MedDi.

Ovadyahu Z.,Hebrew University of Jerusalem
Physical Review B - Condensed Matter and Materials Physics | Year: 2015

This paper describes experiments utilizing a unique property of electron glasses to gain information on the fundamental nature of the interacting Anderson-localized phase. The methodology is based on measuring the energy absorbed by the electronic system from alternating electromagnetic fields as a function of their frequency. Experiments on three-dimensional (3D) amorphous indium-oxide films suggest that, in the strongly localized regime, the energy spectrum is discrete and inelastic electron-electron events are strongly suppressed. These results imply that, at low temperatures, electron thermalization and finite conductivity depend on coupling to the phonon bath. The situation is different for samples nearing the metal-insulator transition; in insulating samples that are close to the mobility edge, energy absorption persists to much higher frequencies. Comparing these results with previously studied 2D samples [Ovadyahu, Phys. Rev. Lett. 108, 156602 (2012)PRLTAO0031-900710.1103/PhysRevLett.108.156602] demonstrates that the mean-level spacing (on a single-particle basis) is not the only relevant scale in this problem. The possibility of delocalization by many-body effects and the relevance of a nearby mobility edge (which may be a many-body edge) are discussed. © 2015 American Physical Society.

Stone N.,Harvard University | Sari R.,Hebrew University of Jerusalem | Loeb A.,Harvard University
Monthly Notices of the Royal Astronomical Society | Year: 2013

The tidal disruption of a star by a supermassive black hole (SMBH) is a highly energetic event with consequences dependent on the degree to whichthe star plunges inside the SMBH's tidal sphere. We introduce a new analytic model for tidal disruption events (TDEs) to analyse the dependence of these events on β, the ratio of the tidal radius to the orbital pericentre.We find, contrary to most previous work, that the spread in debris energy for a TDE is largely constant for all β. This result has important consequences for optical transient searches targeting TDEs, which we discuss. We quantify leading-order general relativistic corrections to this spread inenergy and find that they are small. We also examine the role of stellar spin and find that a combination of spin-orbit misalignment, rapid rotation and high β may alter the spread in debris energy. Finally, we quantify for the firsttime the gravitational wave emission due to the strong compression of a star in a high-β TDE. Although this signal is unlikely to bedetectable for disruptions of main-sequence stars, the tidal disruption of a white dwarf by an intermediate mass black hole can produce a strong signal visible to Advanced LIGO at tens of megaparsecs. © 2013 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.

Horowitz M.,Hebrew University of Jerusalem
Comprehensive Physiology | Year: 2014

Heat acclimation is a within-life phenotypic adaptation to heat. Plasticity of the thermoregulatory system is crucial for the induction of heat acclimation. In the last two decades, it has become clear that heat causes adaptive shifts in gene expression which adjust the protein balance. These changes are part of the evolvement of the acclimated phenotype. The molecular-cellular aspects of some acclimatory mechanisms that have only been explained by physiological-effectorial mechanisms have been discovered. This review attempts to bridge the gap between the classic physiological heat acclimation profile and the molecular/cellular mechanisms underlying the evolvement of the acclimated phenotype. Heat acclimation leads to leftward and rightward shifts in temperature thresholds of heat dissipation organs and thermal injury, respectively, thereby expanding the acclimated dynamic thermoregulatory range. Interactions between ambient temperature and afferent drives from effector organs to the hypothalamic thermoregulatory center with modifications in warm/cold sensitive neuron ratio and excitability contribute to the threshold changes. The altered threshold for thermal injury is associated with progressive enhancement of inducible cytoprotective networks, including HSP70, HSF1, and HIF-1α. These molecules are also important in acclimatory kinetics. Aspects of cross-adaption, cross-tolerance and interference with heat acclimation are explained using molecular-cellular physiological interactions, with the heart, skeletal muscles, and water secretory glands as models. Lastly, the roles of epigenetic mechanisms in transcriptional regulation during induction of the acclimated phenotype, its decay, and reinduction are discussed. Posttranslational histone modifications in the promoters of hsp70 and hsp90 form part of our prototype model of heat-acclimation-mediated cytoprotective memory. © 2014 American Physiological Society.

Veledina A.,University of Oulu | Poutanen J.,University of Oulu | Vurm I.,Hebrew University of Jerusalem
Monthly Notices of the Royal Astronomical Society | Year: 2013

Multiwavelength observations of Galactic black hole transients have opened a new path to understanding the physics of the innermost parts of the accretion flows. While the processes giving rise to their X-ray continuum have been studied extensively, the emission in the optical and infrared (OIR) energy bands was less investigated and remains poorly understood. The standard accretion disc, which may contribute to the flux at these wavelengths, is not capable of explaining a number of observables: the infrared excesses, fast OIR variability and a complicated correlation with the X-rays. It was suggested that these energy bands are dominated by the jet emission; however, this scenario does not work in a number of cases. We propose here an alternative, namely that most of the OIR emission is produced by the extended hot accretion flow. In this scenario, the OIR bands are dominated by the synchrotron radiation from the non-thermal electrons. An additional contribution is expected from the outer irradiated part of the accretion disc heated by the X-rays. We discuss the properties of the model and compare them to the data. We show that the hot-flow scenario is consistent with many of the observed spectral data, at the same time naturally explaining X-ray timing properties, fast OIR variability and its correlation with the X-rays. © 2013 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.

Gal A.,Hebrew University of Jerusalem
Nuclear Physics A | Year: 2010

Oscillatory behavior of electron capture rates in the two-body decay D→R+ν of hydrogen-like ion into recoil ion plus undetected neutrino ν, with a period of approximately 7 s, was reported in storage ring single-ion experiments at the GSI Laboratory, Darmstadt. Ivanov and Kienle [A.N. Ivanov, P. Kienle, Phys. Rev. Lett. 103 (2009) 062502] have relegated this period to neutrino masses through neutrino mixing in the final state. New arguments are given here against this interpretation, while suggesting that these 'GSI Oscillations' may be related to neutrino spin precession in the static magnetic field of the storage ring. This scenario requires a Dirac neutrino magnetic moment μν six times lower than the Borexino solar neutrino upper limit of 0.54×10-10μB [C. Arpesella, et al., Borexino Collaboration, Phys. Rev. Lett. 101 (2008) 091302], and its consequences are briefly explored. © 2010 Elsevier B.V.

Dekel A.,Hebrew University of Jerusalem | Krumholz M.R.,University of California at Santa Cruz
Monthly Notices of the Royal Astronomical Society | Year: 2013

We predict the evolution of giant clumps undergoing star-driven outflows in high-z gravitationallyunstable disc galaxies.We find that themass-loss is expected to occur through a steadywind over many tens of free-fall times (tff ~ 10 Myr) rather than by an explosive disruption inone or a few tff. Our analysis is based on the finding from simulations that radiation trapping isnegligible because it destabilizes the wind (Krumholz & Thompson 2012, 2013). Each photoncan therefore contribute to the wind momentum only once, so the radiative force is limitedto L/c. When combining radiation, protostellar and main-sequence winds, and supernovae,we estimate the total direct injection rate of momentum into the outflow to be 2.5 L/c. Theadiabatic phase of supernovae and main-sequence winds can double this rate. The resultingoutflow mass-loading factor is of order unity, and if the clumps were to deplete their gas, thetime-scale would have been a few disc orbital times, to end with half the original clump massin stars. However, the clump migration time to the disc centre is of the order of an orbital time,about 250 Myr, so the clumps are expected to complete their migration prior to depletion. Furthermore,the clumps are expected to double their mass in a disc orbital time by accretion fromthe disc and clump-clump mergers, so their mass actually grows in time and with decreasingradius. From the six to seven giant clumps with observed outflows, five are consistent withthese predictions, and one has a much higher mass-loading factor and momentum injectionrate. The latter either indicates that the estimated outflow is an overestimate (within the 1serror), that the star formation rate has dropped since the time when the outflow was launchedor that the driving mechanism is different, e.g. supernova feedback in a cavity generated bythe other feedbacks. © 2013 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.

Bekenstein J.D.,Hebrew University of Jerusalem
Foundations of Physics | Year: 2014

I propose an experiment that may be performed, with present low temperature and cryogenic technology, to reveal Wheeler's quantum foam. It involves coupling an optical photon's momentum to the center of mass motion of a macroscopic transparent block with parameters such that the latter is displaced in space by approximately a Planck length. I argue that such displacement is sensitive to quantum foam and will react back on the photon's probability of transiting the block. This might allow determination of the precise scale at which quantum fluctuations of space-time become large, and so differentiate between the brane-world and the traditional scenarios of spacetime. © 2014 Springer Science+Business Media New York.

Abeliovich H.,Hebrew University of Jerusalem
Amino Acids | Year: 2015

Autophagy is a catabolic membrane-trafficking process that occurs in all eukaryotic organisms analyzed to date. The study of autophagy has exploded over the last decade or so, branching into numerous aspects of cellular and organismal physiology. From basic functions in starvation and quality control, autophagy has expanded into innate immunity, aging, neurological diseases, redox regulation, and ciliogenesis, to name a few roles. In the present review, I would like to narrow the discussion to the more classical roles of autophagy in supporting viability under nutrient limitation. My aim is to provide a semblance of a historical overview, together with a concise, and perhaps subjective, mechanistic and functional analysis of the central questions in the autophagy field. © 2014 Springer-Verlag Wien.

Sharon G.,Hebrew University of Jerusalem
Quaternary International | Year: 2010

Acheulian biface industries based on the production of large flakes as the primary blank used for handaxe and cleaver manufacturing have long been acknowledged in the study of the African Acheulian. Nevertheless, this group of assemblages has not received its due attention in the study of the Acheulian techno-complex. The aim of this paper is to define the " Large Flake" stage of the Acheulian, based on the study of thousands of bifacial tools from almost all regions in which Acheulian assemblages have been reported. Once a definition is presented, the large flake Acheulian geographical distribution, chronological boundaries and, in particular, significance to the understanding of the Acheulian as the widest spread and longest existing techno-complex in human cultural evolution are discussed. © 2009 Elsevier Ltd and INQUA.

Rosenfeld D.,Hebrew University of Jerusalem
Atmospheric Research | Year: 2013

The Arctic Oscillation (AO) has been found in previous studies to be a major synoptic factor affecting the climate of many regions in the high and mid-latitudes. This paper demonstrates the physical process by which the AO affects the climate of the Eastern Mediterranean basin, with a focus on precipitation in Israel as a case study.It is shown that a trend of increasing AO is associated with a substantial decrease of winter precipitation from the Iberian Peninsula, though Italy, Greece, Turkey and Cyprus, as well as Lebanon, Syria and also the northern parts of Israel. Winter rain is slightly increased in the southern coast of the eastern half of the Mediterranean Sea. The immediate meteorological causes are shown to be a larger northerly component of the flow over the Mediterranean Sea, associated with a decreasing relative humidity and stability, except over the southern coast, where the air mass has the longest track over the relatively warm water. We suggest here that the observed changes in air flow that drives the precipitation trends can be explained by shifts in the AO that can be partially explained by increasing greenhouses gases. Results from the IPCC multi climate models show that the AO will continue to increase during the 21st century. This increase may lead to a continuation of the trends discussed here.The importance of the analysis provided here is in pointing out the possibility that processes that have been predicted by global warming and changes in global circulation have already started to affect precipitation and major water resources in the Mediterranean basin. © 2013 Elsevier B.V.

Gordon O.,Hebrew University of Jerusalem
Arteriosclerosis, thrombosis, and vascular biology | Year: 2012

Proangiogenic therapy is a promising avenue for the treatment for chronic heart failure and a potentially powerful modality for reversing adverse cardiac remodeling. There is a concern, however, that adverse remodeling might enter an irreversible stage, and become refractory to treatments. The present study aims to determine whether neovascularization therapy is feasible at end stage heart failure and its capacity to reverse adverse cardiac remodeling during progressive disease stages. Using a conditional transgenic mouse system for generating escalating levels of myocardium-specific vascular deficit and resultant stepwise development of heart remodeling, we show that left ventricular dilatation and fibrosis precede ventricular hypertrophy, but that interstitial fibrosis is progressive and eventually results in heart failure. Vascular endothelial growth factor-mediated neovascularization was efficient even at the end stage of disease, and rescued compromised contractile function. Remarkably, remodeling was also fully reversed by neovascularization during early and late stages. Adverse remodeling could not be rescued, however, at the end stage of the disease, thus defining a point of no return and indentifying a critical level of fibrosis as the key determinant to be considered in intended reversal. The study supports the notion of a restricted golden time for remodeling reversal but not for vascular endothelial growth factor-induced neovascularization, which is feasible even during advanced disease stages.

Friedman E.,Hebrew University of Jerusalem
Nuclear Physics A | Year: 2014

Experimental annihilation cross sections of antineutrons and antiprotons at very low energies are compared. Features of Coulomb focusing are observed for p- annihilation on protons. Direct comparisons for heavier targets are not straightforward due to lack of overlap between targets and energies of experimental results for p- and nNevertheless, the annihilation cross sections for n- on nuclei cannot be described by an optical potential that fits well all the available data on p- interactions with nuclei. Comparisons made with the help of this potential reveal in the n- data features similar to Coulomb focusing. Direct comparisons between n- and p- annihilations at very low energies would be possible when p- cross sections are measured on the same targets and at the same energies as the available cross sections for n Such measurements may be possible in the foreseeable future. © 2014 Elsevier B.V.

A few extremely halophilic Archaea (Halobacterium salinarum, Haloquadratum walsbyi, Haloferax mediterranei, Halorubrum vacuolatum, Halogeometricum borinquense, Haloplanus spp.) possess gas vesicles that bestow buoyancy on the cells. Gas vesicles are also produced by the anaerobic endospore-forming halophilic Bacteria Sporohalobacter lortetii and Orenia sivashensis. We have extensive information on the properties of gas vesicles in Hbt. salinarum and Hfx. mediterranei and the regulation of their formation. Different functions were suggested for gas vesicle synthesis: buoying cells towards oxygen-rich surface layers in hypersaline water bodies to prevent oxygen limitation, reaching higher light intensities for the light-driven proton pump bacteriorhodopsin, positioning the cells optimally for light absorption, light shielding, reducing the cytoplasmic volume leading to a higher surface-area-to-volume ratio (for the Archaea) and dispersal of endospores (for the anaerobic spore-forming Bacteria). Except for Hqr. walsbyi which abounds in saltern crystallizer brines, gas-vacuolate halophiles are not among the dominant life forms in hypersaline environments. There only has been little research on gas vesicles in natural communities of halophilic microorganisms, and the few existing studies failed to provide clear evidence for their possible function. This paper summarizes the current status of the different theories why gas vesicles may provide a selective advantage to some halophilic microorganisms. © 2013 by the authors; licensee MDPI, Basel, Switzerland.

London N.,University of California at San Francisco | Raveh B.,University of California at San Francisco | Schueler-Furman O.,Hebrew University of Jerusalem
Current Opinion in Chemical Biology | Year: 2013

Protein Interactions (PPIs) mediate numerous biological functions. As such, the inhibition of specific PPIs has tremendous therapeutic value. The notion that these interactions are 'undruggable' has petered out with the emergence of more and more successful examples of PPI inhibitors, expanding considerably the scope of potential drug targets. The accumulated data on successes in the inhibition of PPIs allow us to analyze the features that are required for such inhibition. Whereas it has been suggested and shown that targeting hot spots at PPI interfaces is a good strategy to achieve inhibition, in this review we focus on the notion that the most amenable interactions for inhibition are those that are mediated by a 'hot segment', a continuous epitope that contributes the majority of the binding energy. This criterion is both useful in guiding future target selection efforts, and in suggesting immediate inhibitory candidates - the dominant peptidic segment that mediates the targeted interaction. © 2013 Elsevier Ltd.

Moll I.,University of Vienna | Engelberg-Kulka H.,Hebrew University of Jerusalem
Trends in Biochemical Sciences | Year: 2012

The bacterial stress response, a strategy to cope with environmental changes, is generally known to operate on the transcriptional level. Here, we discuss a novel paradigm for stress adaptation at the post-transcriptional level, based on the recent discovery of a stress-induced modified form of the translation machinery in Escherichia coli that is generated by MazF, the toxin component of the toxin-antitoxin (TA) module mazEF. Under stress, the induced endoribonuclease MazF removes the 3'-terminal 43 nucleotides of the 16S rRNA of ribosomes and, concomitantly, the 5'-untranslated regions (UTRs) of specific transcripts. This elegant mechanism enables selective translation due to the complementary effect of MazF on ribosomes and mRNAs, and also represents the first example of functional ribosome heterogeneity based on rRNA alteration. © 2012 Elsevier Ltd.

Dvir-Ginzberg M.,Hebrew University of Jerusalem | Steinmeyer J.,Justus Liebig University
Frontiers in Bioscience | Year: 2013

Osteoarthritis (OA) is a degenerative joint disease particularly affecting the elderly population. Although several genetic features have been characterized as risk factors for OA susceptibility, a growing body of evidence indicates that epigenetic effectors may also modulate gene expression and thus contribute to OA pathology. One such epigenetic regulator of particular relevance to OA is Silent Information Regulator 2 type 1 (SirT1) which has been linked to aging and caloric intake, Consistently, SirT1 has been also connected with various age-associated diseases such as diabetes type II, Alzheimers and osteoporosis. Recent reports show that OA is linked to changes in SirT1 activity or levels within cartilage. In human chondrocytes, SirT1 plays a role in cartilage extracellular matrix (ECM) synthesis and promotes cell survival, even under proinflammatory stress. It appears that SirT1 fine tunes many cellular biochemical processes through its capacity to interact and modify various histone and non-histone proteins. Taken together these investigations demonstrate that SirT1 is involved in cartilage biology and could potentially serve as novel drug target in treating OA even at its premature stages, thereby possibly reversing mechanical-stress induced cartilage degeneration.

Cernea S.,Nutrition and Metabolic Diseases Outpatient Unit | Itamar R.A.Z.,Hebrew University of Jerusalem
Diabetes Care | Year: 2011

The complex pathological mechanisms responsible for development of type 2 diabetes are not fully addressed by conventional drugs, which are also associated with inconvenient side effects such as weight gain or hypoglycemia. Two types of incretin-based therapies are now in use: incretin mimetics (glucagon-like peptide-1 [GLP-1] receptor agonists that bind specific receptors and mimic the action of natural GLP-1) and incretin enhancers (inhibitors of the enzyme that degrade the incretin hormones and thus prolong their activity). Both offer important advantages over previous agents. In addition to the proven glucose-lowering efficacy, they promote weight loss (or are weight neutral) by slowing gastric emptying and inducing satiety, inhibit glucagon secretion with maintenance of counterregulatory mechanisms, and exhibit cardiovascular benefits, while having a low risk profile. Importantly, short-term studies have shown that incretins/incretin-based therapies protect β-cells (by enhancing cell proliferation and differentiation and inhibiting apoptosis) and stimulate their function (by recruiting β-cells to the secretory process and increasing insulin biosynthesis/secretion). These therapies have the opportunity to interfere with the disease progression if used as an early intervention, when enough β-cell mass/function can still be preserved or restored. © 2011 by the American Diabetes Association.

Gal A.,Hebrew University of Jerusalem | Millener D.J.,Brookhaven National Laboratory
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2011

It is shown how the recent shell-model determination of λN spin-dependent interaction terms in λ hypernuclei allows for a reliable deduction of ΛΛ separation energies in ΛΛ hypernuclei across the nuclear p shell. Comparison is made with the available data, highlighting BeΛΛ11 and BeΛΛ12 which have been suggested as possible candidates for the KEK-E373 HIDA event. © 2011 Elsevier B.V.

Marcus Y.,Hebrew University of Jerusalem
Journal of Physical Chemistry B | Year: 2014

The standard partial molar volumes of 16 polyatomic more-or-less globular anions in aqueous solutions at 25 °C were calculated as the sum of the intrinsic and (negative) electrostrictive volumes and compared with the experimental values. The intrinsic volumes used an empirical additive to the bare ionic radius to account for void spaces near the ions. The volume shrinkage due electrostriction was calculated according to the shell-by-shell electrostatic method. Agreement for many of the anions was achieved, but in some cases, notably the trivalent phosphate and arsenate ones, the calculated values failed to reproduce the experimental ones within reasonable uncertainties of the sizes of the anions. © 2014 American Chemical Society.

Jimenez G.,Catalan Institution for Research and Advanced Studies | Shvartsman S.Y.,Princeton University | Paroush Z.,Hebrew University of Jerusalem
Journal of Cell Science | Year: 2012

Receptor tyrosine kinase (RTK) signaling pathways control multiple cellular decisions in metazoans, often by regulating the expression of downstream genes. In Drosophila melanogaster and other systems, E-twenty-six (ETS) transcription factors are considered to be the predominant nuclear effectors of RTK pathways. Here, we highlight recent progress in identifying the HMG-box protein Capicua (CIC) as a key sensor of RTK signaling in both Drosophila and mammals. Several studies have shown that CIC functions as a repressor of RTK-responsive genes, keeping them silent in the absence of signaling. Following the activation of RTK signaling, CIC repression is relieved, and this allows the expression of the targeted gene in response to local or ubiquitous activators. This regulatory switch is essential for several RTK responses in Drosophila, from the determination of cell fate to cell proliferation. Furthermore, increasing evidence supports the notion that this mechanism is conserved in mammals, where CIC has been implicated in cancer and neurodegeneration. In addition to summarizing our current knowledge on CIC, we also discuss the implications of these findings for our understanding of RTK signaling specificity in different biological processes. © 2012.

Bank E.M.,Hebrew University of Jerusalem
Nucleus (Austin, Tex.) | Year: 2011

The nuclear lamina is a protein-rich network located directly underneath the inner nuclear membrane of metazoan nuclei. The components of the nuclear lamina have been implicated in nearly all nuclear functions; therefore, understanding the structural, mechanical, and signal transducing properties of these proteins is crucial. In addition, mutations in many of these proteins cause a wide range of human diseases, the laminopathies. The structure, function, and interaction of the lamina proteins are conserved among metazoans, emphasizing their fundamental roles in the nucleus. Several of the advances in the field of the nuclear lamina have come from studies performed in Caenorhabditis elegans or on C. elegans proteins expressed in vitro. Here, we discuss the current knowledge about the nuclear lamina, including an overview of the technical tools offered by C. elegans that make it a powerful model organism for the study of the nuclear lamina and laminopathic diseases.

Butler R.,Hebrew University of Jerusalem
Advances in Child Development and Behavior | Year: 2014

Girls and women now outperform boys and men on many indices of academic achievement. Gender differences in motivation may underlie these trends. In this chapter, I review and integrate research on gender differences in self-evaluation, self-regulation, and achievement goals. I argue for the existence of gendered tendencies "to prove" versus "to try and to improve," whereby males tend to orient to demonstrating and defending their abilities, and females to working hard and addressing deficiencies. I discuss how these motivations develop within social and educational contexts of learning, and intersect with gendered patterns of socialization, values, and behaviors in other arenas, especially relational ones. Recurring themes include the costs and benefits of differential emphases on competition and self-promotion versus affiliation and consideration of others in the family, peer group, and classroom. I conclude with some recommendations for creating classroom environments that might promote optimal motivation among all students, regardless of gender. © 2014 Elsevier Inc.

Hazan T.,Toyota USA | Shashua A.,Hebrew University of Jerusalem
IEEE Transactions on Information Theory | Year: 2010

Inference problems in graphical models can be represented as a constrained optimization of a free-energy function. In this paper, we treat both forms of probabilistic inference, estimating marginal probabilities of the joint distribution and finding the most probable assignment, through a unified message-passing algorithm architecture. In particular we generalize the belief propagation (BP) algorithms of sum-product and max-product and tree-reweighted (TRW) sum and max product algorithms (TRBP) and introduce a new set of convergent algorithms based on "convex-free-energy" and linear-programming (LP) relaxation as a zero-temperature of a convex-free-energy. The main idea of this work arises from taking a general perspective on the existing BP and TRBP algorithms while observing that they all are reductions from the basic optimization formula of f + Σ ih i where the function f is an extended-valued, strictly convex but nonsmooth and the functions h i are extended-valued functions (not necessarily convex). We use tools from convex duality to present the "primal-dual ascent" algorithm which is an extension of the Bregman successive projection scheme and is designed to handle optimization of the general type f + Σ ih i. We then map the fractional-free-energy variational principle for approximate inference onto the optimization formula above and introduce the "norm-product" message-passing algorithm. Special cases of the norm-product include sum-product and max-product (BP algorithms), TRBP and NMPLP algorithms. When the fractional-free-energy is set to be convex (convex-free-energy) the norm-product is globally convergent for the estimation of marginal probabilities and for approximating the LP-relaxation. We also introduce another branch of the norm-product which arises as the "zero-temperature" of the convex-free-energy which we refer to as the "convex-max-product". The convex-max-product is convergent (unlike max-product) and aims at solving the LP- relaxation. © 2006 IEEE.

Glasner A.,Hebrew University of Jerusalem
PloS one | Year: 2012

Natural killer (NK) cells are innate cytotoxic lymphocytes that specialize in the defense against viral infection and oncogenic transformation. Their action is tightly regulated by signals derived from inhibitory and activating receptors; the later include proteins such as the Natural Cytotoxicity Receptors (NCRs: NKp46, NKp44 and NKp30). Among the NCRs, NKp46 is the only receptor that has a mouse orthologue named Ncr1. NKp46/Ncr1 is also a unique marker expressed on NK and on Lymphoid tissue inducer (LTI) cells and it was implicated in the control of various viral infections, cancer and diabetes. We have previously shown that human NKp46 recognizes viral hemagglutinin (HA) in a sialic acid-dependent manner and that the O-glycosylation is essential for the NKp46 binding to viral HA. Here we studied the molecular interactions between Ncr1 and influenza viruses. We show that Ncr1 recognizes influenza virus in a sialic acid dependent manner and that N-glycosylation is important for this binding. Surprisingly we demonstrate that none of the predicted N-glycosilated residues of Ncr1 are essential for its binding to influenza virus and we thus conclude that other, yet unidentified N-glycosilated residues are responsible for its recognition. We have demonstrated that N glycosylation play little role in the recognition of mouse tumor cell lines and also showed the in-vivo importance of Ncr1 in the control of influenza virus infection by infecting C57BL/6 and BALB/c mice knockout for Ncr1 with influenza.

Gal A.,Hebrew University of Jerusalem | Garcilazo H.,National Polytechnic Institute of Mexico
Physical Review Letters | Year: 2013

The D03 dibaryon is generated dynamically as a resonance pole in a πNΔ′ three body model, where Δ ′ is a stable Δ baryon. Using separable interactions dominated by the Δ(1232) isobar for πN and by the D12(2150) isobar for NΔ′, with D12(2150) the NΔ dibaryon deduced in and constrained by D21 pp scattering, the model reduces to an effective two body problem for ΔΔ′ which is solved. The mass and width of D03 are found close to those of the I(JP)=0(3+) resonance peak observed by WASA-at-COSY in pion-production pn collisions at 2.37 GeV. © 2013 American Physical Society.

Sambanis N.,Yale University | Schulhofer-Wohl J.,Princeton University | Shayo M.,Hebrew University of Jerusalem
Science | Year: 2012

Current U.S. practice in Afghanistan may reify social divisions, which undermines institutions critical to postwar stability.

Binshtok A.M.,Hebrew University of Jerusalem
International Review of Neurobiology | Year: 2011

Many surgical and dental procedures depend on use of local anesthetics to reversibly eliminate pain. By the blockade of voltage-gated sodium channels, local anesthetics prevent the transmission of nociceptive information. However, since all local anesthetics act non-selectively on all types of axons they also cause a loss of innocuous sensation, motor paralysis and autonomic block. Thus, approaches that produce only a selective blockade of pain fibers are of great potential clinical importance. In this chapter we will review the recent findings describing mechanisms of pain transduction and transmission and introduce novel therapeutic approaches to produce pain-selective analgesia. © 2011 Elsevier Inc.

Oren A.,Hebrew University of Jerusalem
Biodiversity and Conservation | Year: 2015

Within the cyanobacterial world there are many species adapted to life in hypersaline environments. Some can even grow at salt concentrations approaching NaCl saturation. Halophilic cyanobacteria often form dense mats in salt lakes, and on the bottom of solar saltern ponds, hypersaline lagoons, and saline sulfur springs, and they may be found in evaporite crusts of gypsum and halite. A wide range of species were reported to live at high salinities. These include unicellular types (Aphanothece halophytica and similar morphotypes described as Euhalothece and Halothece), as well as non-heterocystous filamentous species (Coleofasciculuschthonoplastes, species of Phormidium, Halospirulina tapeticola, Halomicronema excentricum, and others). Cyanobacterial diversity in high-salt environments has been explored using both classic, morphology-based taxonomy and molecular, small subunit rRNA sequence-based techniques. This paper reviews the diversity of the cyanobacterial communities in hypersaline environments worldwide, as well as the physiological adaptations that enable these cyanobacteria to grow at high salt concentrations. To withstand the high osmotic pressure of their surrounding medium, halophilic cyanobacteria accumulate organic solutes: glycine betaine is the preferred solute in the most salt-tolerant types; Coleofasciculus produces the heteroside glucosylglycerol, and the less salt-tolerant cyanobacteria generally accumulate the disaccharides sucrose and trehalose under salt stress. Some cyanobacteria growing in benthic mats in hypersaline environments are adapted to life under anoxic conditions and they can use sulfide as an alternative electron donor in an anoxygenic type of photosynthesis through a process which involves photosystem I only. © 2015, Springer Science+Business Media Dordrecht.

Grusec J.E.,University of Toronto | Davidov M.,Hebrew University of Jerusalem
Child Development | Year: 2010

There are several different theoretical and research approaches to the study of socialization, characterized by frequently competing basic tenets and apparently contradictory evidence. As a way of integrating approaches and understanding discrepancies, it is proposed that socialization processes be viewed from a domain perspective, with each domain characterized by a particular form of social interaction between the object and agent of socialization and by specific socialization mechanisms and outcomes. It is argued that this approach requires researchers to identify the domain of social interaction they are investigating, to understand that phenotypically similar behaviors may belong to different domains, and to acknowledge that caregivers who are effective in one type of interaction may not be effective in another. © 2010, Copyright the Author(s). Journal Compilation © 2010, Society for Research in Child Development, Inc.

Ben-Naim A.,Hebrew University of Jerusalem
Journal of Biomolecular Structure and Dynamics | Year: 2012

Attempts to answer the Levinthal question "How proteins fold to give such a unique structure" are discussed. In the first part of this article, we focus on a few reasons as to why the solution to the protein-folding problem (PFP) has been elusive for a very long time. One is a result of the misinterpretation of Anfinsen's Thermodynamic hypothesis which led to the conclusion that the native structure of a protein must be at a global minimum of the Gibbs energy. The second is the result of the adherence to the hydrophobic paradigm, and at the same time ignoring a whole repertoire of hydrophilic effects. It is argued that switching from a target-based to a caused-based approach, and adopting the hydrophilic paradigm leads straightforwardly to a simple answer to Levinthal's question, as well as to a solution of the PFP. Copyright © 2012 Taylor & Francis.

Agmon N.,Hebrew University of Jerusalem
Physical Chemistry Chemical Physics | Year: 2011

The residence probability of a freely diffusing particle within an open d-dimensional ball is calculated as a function of time, for an initial distribution that is either a spherical delta function or uniform within the sphere. The latter is equivalent to the autocorrelation function (ACF) of fluorescence correlation spectroscopy (FCS) when utilizing near-field scanning optical microscopy (NSOM) probes. Starting from the general equation for the Laplace transform of the residence probability, we solve it in Laplace space for any dimensionality, inverting it into the time domain in one- and three-dimensions. The short- and long-time asymptotic behaviors of the residence probability are derived and compared with the exact results. Approximations for the two-dimensional ACF are discussed, and a new approximation is derived for the NSOM-FCS ACF. Also of interest is an analytic expression for a three-dimensional ACF, which could be useful for two-photon FCS. Analogy with the binding probability for reversible geminate recombination suggests that more information could be extracted from the long-time tails in FCS experiments. © 2011 The Owner Societies.

Asnin V.,Hebrew University of Jerusalem
Journal of High Energy Physics | Year: 2010

Conformal moduli spaces of four-dimensional superconformal theories obtained by deformations of a superpotential are considered. These spaces possess a natural metric (a Zamolodchikov metric). This metric is shown to be Kahler. The proof is based on superconformal Ward identities. © SISSA 2010.

Epelboym I.,Columbia University | Mazeh H.,Hebrew University of Jerusalem
Oncologist | Year: 2014

Zollinger-Ellison syndrome (ZES) is an endocrinopathy characterized by gastrin-secreting tumors, responsible for causing the formation ofmultiple, refractory, and recurrent peptic ulcers in the distal duodenum and proximal jejunum. Two main variants have been described, sporadic and those found in association with parathyroid andpituitary tumors, a genetic disorder known asmultiple endocrine neoplasia-1 (MEN-1). Biochemical serum evaluation for elevated gastrin, followed by radiological or nuclear localization of the primary lesion, is mandated for establishing diagnosis. The mainstays of treatment include management of hypersecretory state withmedical suppression of gastric acid production and surgical resection of primary tumor for the prevention of malignant transformation and metastatic complications. Medical therapy with proton pump inhibitors has virtually eliminated the need for acid-reducing surgical procedures. Surgical approach to sporadic and MEN-1- associated ZES varies based on our understanding of the natural history of the condition and the probability of cure; however, resection to a negative microscopic margin is indicated in both cases. Postoperative surveillance involves measurement of gastrin level, followed by imaging if elevation is detected. Reexcision of recurrent or resection of metastatic disease is a subject of controversy; however, at the present time aggressive cytoreductive approachis favored. © AlphaMed Press 2014.

Heyman S.N.,Hebrew University of Jerusalem
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association | Year: 2012

Hypoxia plays a role in ischemic, toxic and sepsis-induced acute kidney injury. Evolving hypoxia triggers renal adaptive responses that may mitigate the insult, leading to sublethal forms of cell injury. The unique capability of the kidney to downregulate oxygen consumption for tubular transport could represent one such adaptive response which promotes maintenance of renal oxygenation, thereby preserving cellular integrity. Tran et al. recently explored a novel mechanism that might prevent tubular damage by downregulation of mitochondrial biogenesis and oxygen consumption. Using expression profiling of kidney RNA in endotoxemic rodents and complementary studies in vitro and in PGC-1α knockout mice, they found a sepsis-related decline in PPARγ coactivator-1α (PGC-1α) expression and of PGC-1α-dependent genes involved in oxidative phosphorylation. This response may explain their observation of a paradoxical preservation of kidney oxygenation and structural integrity in sepsis, despite reduced renal blood flow and oxygen delivery. Thus, resetting of mitochondrial respiration and oxygen consumption during sepsis might be added to the growing list of adaptive responses that occur during hypoxic stress. This review will focus on these mechanisms that mitigate evolving hypoxic injury, even at the expense of transient renal dysfunction.

Type IV pili (Tfp) play a primary role in mediating the adherence of pathogenic bacteria to their hosts. The pilus filament can retract with an immense force. However, the role of this activity in microbial pathogenesis has not been rigorously explored. Experiments performed on volunteers suggested that the retraction capacity of enteropathogenic Escherichia coli (EPEC) Tfp is required for full virulence. Here we review our recent study(1) in which we showed that the retraction capacity of the EPEC Tfp facilitates tight-junction disruption and actin-rich pedestal formation by promoting efficient bacterial protein effector translocation into epithelial host cells. We also present new data using live imaging confocal microscopy suggesting that EPEC adheres to monolayers in microcolonies and that Tfp retraction facilitates significant changes in the microcolony shape, which may be critical for efficient effector delivery. Our studies hence suggest novel insights into the role of pili retraction in EPEC pathogenesis.

Krolik J.H.,Johns Hopkins University | Piran T.,Hebrew University of Jerusalem
Astrophysical Journal | Year: 2012

Tidal disruption of main-sequence stars by black holes has generally been thought to lead to a signal dominated by UV emission. If, however, the black hole spins rapidly and the poloidal magnetic field intensity on the black hole horizon is comparable to the inner accretion disk pressure, a powerful jet may form whose luminosity can easily exceed the thermal UV luminosity. When the jet beam points at Earth, its non-thermal luminosity can dominate the emitted spectrum. The thermal and non-thermal components decay differently with time. In particular, the thermal emission should remain roughly constant for a significant time after the period of maximum accretion, beginning to diminish only after a delay, whereas after the peak accretion rate, the non-thermal jet emission decays, but then reaches a plateau. Both transitions are tied to a characteristic timescale t Edd at which the accretion rate falls below Eddington. Making use of this timescale in a new parameter-inference formalism for tidal disruption events with significant emission from a jet, we analyze the recent flare source Swift J2058. It is consistent with an event in which a main-sequence solar-type star is disrupted by ∼ a black hole of mass 4 × 107 M ⊙. The beginning of the flat phase in the non-thermal emission from this source can possibly be seen in the late-time light curve. Optical photometry over the first ≃ 40days of this flare is also consistent with this picture, but is only weakly constraining because the bolometric correction is very uncertain. We suggest that future searches for main-sequence tidal disruptions use methods sensitive to jet radiation as well as to thermal UV radiation. © © 2012. The American Astronomical Society. All rights reserved.

Cohen-Carmon D.,Hebrew University of Jerusalem
Nucleus (Austin, Tex.) | Year: 2012

Polyglutamine (PolyQ)-related diseases are dominant late-onset genetic disorders that are manifested by progressive neurodegeneration, leading to behavioral and physical impairments. An increased body of evidence suggests that chromatin structure and epigenetic regulation are involved in disease pathology. PolyQ diseases often display an aberrant transcriptional regulation due to the disrupted function of histone-modifying complexes and altered interactions of the polyQ-extended proteins with chromatin-related factors. In this review we describe recent findings relating to the role of chromatin in polyQ diseases. We discuss the involvement of epigenetic-related factors and chromatin structure in genomic instability of CAG repeats; we describe changes in the expression and regulation of chromatin-related enzymes and in the levels and patterns of histone modifications in disease state; we illustrate the potential beneficial effects of different histone deacetylase (HDAC) inhibitors for the treatment of polyQ diseases, and we end by describing the potential use of human pluripotent stem cells and their differentiated derivatives for modeling polyQ diseases in vitro. Taken together, these accumulating studies strongly suggest that disrupted chromatin regulation may be directly involved with the pathophysiology of polyQ-related diseases.

Bekenstein J.D.,Hebrew University of Jerusalem
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

Diverse calculations have shown that a relativistic field confined to a cavity by well-defined boundary conditions can have a negative Casimir or vacuum energy. Why then can one not make a finite system with negative mass by confining the field in some way? We recall, and justify in detail, the not so familiar subdominant trace energy condition for ordinary (baryon-electron nonrelativistic) matter. With its help we show, in two ways, that the mass energy of the cavity structure necessary to enforce the boundary conditions must exceed the magnitude of the negative vacuum energy, so that all systems of the type envisaged necessarily have positive mass energy. © 2013 American Physical Society.

Marcus Y.,Hebrew University of Jerusalem
Chemical Reviews | Year: 2013

The internal pressure describes the change in the energy on incremental isothermal expansion where the intermolecular distances increase slightly without major disruption of the attractive forces between the molecules. This view, then, accounts for the very small n values for the highly hydrogen-bonded water and hydrogen fluoride and the small n values for alkanols and other protic liquids as well as aprotic dipolar liquids with large dipole moments. A large number of other binary systems have been studied over the years by noting their internal pressures as functions of the compositions, those presented above being just representative examples. Reactions proceeding in solution are affected by many factors, and the authors have searched the most effective ones in order to promote the favorable outcome of the reactions in terms of their rates or the nature of the products.

Samach A.,Hebrew University of Jerusalem
Annals of Botany | Year: 2013

BackgroundStudying a process in a new species often relies on focusing our attention to a candidate gene, encoding a protein similar to one with a known function. Not all the choices seem to be prudent.ScopeThis Viewpoint includes an overview of issues that are encountered during research of candidate genes. Defining a match for a gene of interest, deciding whether variation in ESTs or RNAseq data for a certain transcript, represent more than one gene. The problem of incorrect annotation of genes due to incorrect in-silico splicing, is also mentioned. The author's humble opinion on how to deal with these issues is provided.ConclusionsThe vast amount of new sequence data provides us with great possibilities for giant leaps in our understanding. Still, we cannot afford to skip over the tedious steps required to confirm that we are indeed studying the correct gene, and try to be sure that the complex expression pattern we observe is not a composite of several genes. © The Author 2012. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved.

Itin Y.,Hebrew University of Jerusalem | Itin Y.,Jerusalem College of Technology
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

The axion modification of electrodynamics can be considered as produced by an irreducible part of the constitutive pseudotensor. In this paper, we study the modification of wave propagation produced by the second irreducible part, called the skewon. We introduce the notions of the skewon optic tensor and skewon optic covector. With these devices we prove that in a pseudo-Riemannian manifold endowed with an arbitrary skewon at least one solution of the dispersion relation is spacelike. This means that the skewon generates superluminal wave motion and is thus ruled out on the basis of special-relativistic principles. © 2013 American Physical Society.

Malinsky-Buller A.,Hebrew University of Jerusalem
Quaternary International | Year: 2015

Over the last 150 years, the Paleolithic era was divided into the Lower, Middle and Upper Paleolithic. This scheme is an arbitrary research construct that confounds chronological, behavioral, and evolutionary meanings. Transitions between these discrete units, and in particular the Lower/Middle Paleolithic transition, received lesser attention.At present, the Lower/Middle Paleolithic transition is still depicted as a worldwide change from biface production to Levallois technology, similar to the way it has been perceived in the initial stages of research. Some key questions remain open for further inquiry: What changed technologically and typologically beyond those guide fossils? What is the geographical variation of this global change(s)? Did changes occur as a result of autochthonous developments in each region or by a diffusion wave (s)? What is the societal process(es) that promoted this evolutionary change?In this paper, I explore the techno-typological variations (reduction sequences and tool kits) in Europe north of the Pyrenees and how these traits pattern diachronically and spatially in the interval of MIS 9-7, the period during which the transition between Lower and Middle Paleolithic is suggested to occur. The first step will be to describe the range of behaviors that existed during each MIS. The presentation of those variants will track the decision-making processes within reduction sequences. The techno-typological variants will be studied in relation to their relative abundance within each assemblage. Then, I will attempt to estimate if observed changes in those traits resulted from a continuous processes or whether the record constitutes of segmented local histories. © 2015 Elsevier Ltd and INQUA.

Etgar L.,Hebrew University of Jerusalem
Materials | Year: 2013

Photovoltaic cells use semiconductors to convert sunlight into electrical current and are regarded as a key technology for a sustainable energy supply. Quantum dot-based solar cells have shown great potential as next generation, high performance, low-cost photovoltaics due to the outstanding optoelectronic properties of quantum dots and their multiple exciton generation (MEG) capability. This review focuses on QDs as light harvesters in solar cells, including different structures of QD-based solar cells, such as QD heterojunction solar cells, QD-Schottky solar cells, QD-sensitized solar cells and the recent development in organic-inorganic perovskite heterojunction solar cells. Mechanisms, procedures, advantages, disadvantages and the latest results obtained in the field are described. To summarize, a future perspective is offered. © 2013 by the authors.

Krumholz M.R.,University of California at Santa Cruz | Dekel A.,Hebrew University of Jerusalem
Astrophysical Journal | Year: 2012

The star formation rates (SFRs) of low-metallicity galaxies depend sensitively on the gas metallicity, because metals are crucial to mediating the transition from intermediate-temperature atomic gas to cold molecular gas, a necessary precursor to star formation. We study the impact of this effect on the star formation history of galaxies. We incorporate metallicity-dependent star formation and metal enrichment in a simple model that follows the evolution of a halo main progenitor. Our model shows that including the effect of metallicity leads to suppression of star formation at redshift z > 2 in dark halos with masses ≲ 1011 M⊙, with the suppression becoming near total for halos below 109.5-1010 M⊙. We find that at high redshift, until z 2, the SFR cannot catch up with the gas inflow rate (IR), because the SFR is limited by the free-fall time, and because it is suppressed further by a lack of metals in small halos. As a result, in each galaxy the SFR is growing in time faster than the IR, and the integrated cosmic SFR density is rising with time. The suppressed in situ SFR at high-z makes the growth of stellar mass dominated by ex situ SFR, meaning stars formed in lower mass progenitor galaxies and then accreted, which implies that the specific SFR (sSFR) remains constant with time. The intensely accreted gas at high-z is accumulating as an atomic gas reservoir. This provides additional fuel for star formation in 1010-1012 M⊙ halos at z 1-3, which allows the SFR to exceed the instantaneous IR, and may enable an even higher outflow rate. At z < 1, following the natural decline in IR with time due to the universal expansion, the SFR and sSFR are expected to drop. We specify the expected dependence of sSFR and metallicity on stellar mass and redshift. At a given z, and below a critical mass, these relations are predicted to be flat and rising, respectively. Our model predictions qualitatively match some of the puzzling features in the observed star formation history. © 2012. The American Astronomical Society. All rights reserved.

Many psychiatric disorders are highly heritable and may represent the clinical outcome of early aberrations in the formation of neural networks. The placement of brain connectivity as an ‘intermediate phenotype’ renders it an attractive target for exploring its interaction with genomics and behavior. Given the complexity of genetic make up and phenotypic heterogeneity in humans, translational studies are indicated. Recently, we demonstrated that a mouse model with heterozygous knockout of the key neurodevelopmental gene Ahi1 displays a consistent stress-resilient phenotype. Extending these data, the current research describes our multi-faceted effort to link early variations in Ahi1 expression with long-term consequences for functional brain networks and cognitive-emotional phenotypes. By combining behavioral paradigms with graph-based analysis of whole-brain functional networks, and then cross-validating the data with robust neuroinformatic data sets, our research suggests that physiological variation in gene expression during neurodevelopment is eventually translated into a continuum of global network metrics that serve as intermediate phenotypes. Within this framework, we suggest that organization of functional brain networks may result, in part, from an adaptive trade-off between efficiency and resilience, ultimately culminating in a phenotypic diversity that encompasses dimensions such as emotional regulation and cognitive function.Molecular Psychiatry advance online publication, 29 March 2016; doi:10.1038/mp.2016.29. © 2016 Macmillan Publishers Limited

Jacobson R.L.,Hebrew University of Jerusalem
Vector-Borne and Zoonotic Diseases | Year: 2011

Leishmaniasis is endemic in the Middle East, and both cutaneous and visceral forms are reported from the region ranging from the Levant to Afghanistan. The potential and proven phlebotomine sand fly vectors and reservoir hosts of the Leishmaniases species in Afghanistan, Iran, Iraq, Israel, Jordan, Lebanon, Saudi Arabia, Syria, Turkey, and Yemen are described. This region has seen a movement of populations across the area, due to both military and civilian strife. Refugees, armed forces, and multi-national contractors are particularly at risk to acquire this disease. There has been an upsurge in Leishmaniasis research, especially as new foci are exposed and the need to protect the naïve populations moving into endemic areas becomes a public health priority. New sand fly vectors and animal reservoirs have been discovered while novel control methods are being evaluated. Modern molecular techniques are now being used more routinely and revealing some unusual findings. The aim of this review is to collate the lost recent data on the burden of the disease, diagnostic applications, eco-epidemiology of vectors, and reservoir hosts, and how the control projects have been developing in the Middle East. © Copyright 2011, Mary Ann Liebert, Inc. 2011.

Marcus Y.,Hebrew University of Jerusalem
Journal of Physical Organic Chemistry | Year: 2012

Binary liquid mixtures of acetonitrile (AN) and water (W) are widely used as reaction media in such fields of chemistry as physical organic chemistry, reverse phase liquid chromatography, and electrochemistry, among others. Much information on the structure of these systems and the interactions in them has accumulated since the author's often quoted comprehensive 1990 paper, so that a review is merited. Macroscopic physical properties, results from diffraction and spectroscopic studies, theoretical considerations and computer simulations, and results from the use of solute probes all bear on the structure (and less so on the dynamics) of the mixtures. These are discussed in terms of the microheterogeneity that occurs in them at intermediate contents (that leads eventually to liquid-liquid phase separation). Copyright © 2012 John Wiley & Sons, Ltd.

Peripheral injury can cause abnormal activity in sensory neurons, which is a major factor in chronic pain. Recent work has shown that injury induces major changes not only in sensory neurons but also in the main type of glial cells in sensory ganglia - satellite glial cells (SGCs), and that interactions between sensory neurons and SGCs contribute to neuronal activity in pain models. The main functional changes observed in SGCs after injury are an increased gap junction-mediated coupling among these cells, and augmented sensitivity to ATP. There is evidence that the augmented gap junctions contribute to neuronal hyperexcitability in pain models, but the mechanism underlying this effect is not known. The changes in SGCs described above have been found following a wide range of injuries (both axotomy and inflammation) in somatic, orofacial and visceral regions, and therefore appear to be a general feature in chronic pain. We have found that in cultures of sensory ganglia calcium signals can spread from an SGC to neighboring cells by calcium waves, which are mediated by gap junctions and ATP acting on purinergic P2 receptors. A model is proposed to explain how augmented gap junctions and greater sensitivity to ATP can combine to produce enhanced calcium waves, which can lead to neuronal excitation. Thus this simple scheme can account for several major changes in sensory ganglia that are common to a great variety of pain models. © 2012 Elsevier B.V.

Vasileiou V.,Montpellier University | Granot J.,Open University of Israel | Piran T.,Hebrew University of Jerusalem | Amelino-Camelia G.,University of Rome La Sapienza
Nature Physics | Year: 2015

Wheeler's 'spacetime-foam'picture of quantum gravity (QG) suggests spacetime fuzziness (fluctuations leading to non-deterministic effects) at distances comparable to the Planck length, L Pl â ‰ 1.62 × 10 â '33 cm, the inverse (in natural units) of the Planck energy, E Pl â ‰ 1.22 × 10 19 GeV. The resulting non-deterministic motion of photons on the Planck scale is expected to produce energy-dependent stochastic fluctuations in their speed. Such a stochastic deviation from the well-measured speed of light at low photon energies, c, should be contrasted with the possibility of an energy-dependent systematic, deterministic deviation. Such a systematic deviation, on which observations by the Fermi satellite set Planck-scale limits for linear energy dependence, is more easily searched for than stochastic deviations. Here, for the first time, we place Planck-scale limits on the more generic spacetime-foam prediction of energy-dependent fuzziness in the speed of photons. Using high-energy observations from the Fermi Large Area Telescope (LAT) of gamma-ray burst GRB090510, we test a model in which photon speeds are distributed normally around c with a standard deviation proportional to the photon energy. We constrain the model's characteristic energy scale beyond the Planck scale at >2.8E Pl (>1.6E Pl), at 95% (99%) confidence. Our results set a benchmark constraint to be reckoned with by any QG model that features spacetime quantization. © 2015 Macmillan Publishers Limited. All rights reserved.

Khasin M.,Michigan State University | Kosloff R.,Hebrew University of Jerusalem
Physical Review Letters | Year: 2011

A closed quantum system is defined as completely controllable if an arbitrary unitary transformation can be executed using the available controls. In practice, control fields are a source of unavoidable noise. Can one design control fields such that the effect of noise is negligible on the timescale of the transformation? Complete controllability in practice requires that the effect of noise can be suppressed for an arbitrary transformation. The present study considers a paradigm of control, where the Lie-algebraic structure of the control Hamiltonian is fixed, while the size of the system increases, determined by the dimension of the Hilbert space representation of the algebra. We show that for large quantum systems, generic noise in the controls dominates for a typical class of target transformation; i.e., complete controllability is destroyed by the noise. © 2011 American Physical Society.

Majhi B.R.,Hebrew University of Jerusalem
Journal of High Energy Physics | Year: 2014

In (1 + 1) dimensional hydrodynamics in presence of the gravitational anomalies, the constitutive relations for the stress tensor contain the response parameters C1, C2 and the gravitation anomaly coefficients c g, c w . Here it is shown that they are related by the two relations C1 = 4π 2 c w and C2 = 8π2c g . This agrees with the earlier findings. I argue that the Israel-Hartle-Hawking vacuum is the natural boundary condition which leads to such relation. Finally, the possible physical implications are discussed. © 2014 The Author(s).

Krumholz M.R.,University of California at Santa Cruz | Dekel A.,Hebrew University of Jerusalem | McKee C.F.,University of California at Berkeley
Astrophysical Journal | Year: 2012

Star formation laws are rules that relate the rate of star formation in a particular region, either an entire galaxy or some portion of it, to the properties of the gas, or other galactic properties, in that region. While observations of Local Group galaxies show a very simple, local star formation law in which the star formation rate per unit area in each patch of a galaxy scales linearly with the molecular gas surface density in that patch, recent observations of both Milky Way molecular clouds and high-redshift galaxies apparently show a more complicated relationship in which regions of equal molecular gas surface density can form stars at quite different rates. These data have been interpreted as implying either that different star formation laws may apply in different circumstances, that the star formation law is sensitive to large-scale galaxy properties rather than local properties, or that there are high-density thresholds for star formation. Here we collate observations of the relationship between gas and star formation rate from resolved observations of Milky Way molecular clouds, from kpc-scale observations of Local Group galaxies, and from unresolved observations of both disk and starburst galaxies in the local universe and at high redshift. We show that all of these data are in fact consistent with a simple, local, volumetric star formation law. The apparent variations stem from the fact that the observed objects have a wide variety of three-dimensional size scales and degrees of internal clumping, so even at fixed gas column density the regions being observed can have wildly varying volume densities. We provide a simple theoretical framework to remove this projection effect, and we use it to show that all the data, from small solar neighborhood clouds with masses ∼103 M O to submillimeter galaxies with masses ∼1011 M O, fall on a single star formation law in which the star formation rate is simply 1% of the molecular gas mass per local free-fall time. In contrast, proposed star formation laws in which the star formation timescale is set by the galactic rotation period are inconsistent with the data from the Milky Way and the Local Group, while those in which the star formation rate is linearly proportional to the gas mass above some density threshold fail both in the Local Group and for starburst galaxies. © 2012. The American Astronomical Society. All rights reserved.

Majhi B.R.,Hebrew University of Jerusalem
Journal of High Energy Physics | Year: 2014

The role of Israel-Hartle-Hawking vacuum is discussed for anomalous fluid in presence of both the gauge and gravitational anomalies in (1 + 3) dimensions. I show that imposition of this vacuum condition leads to the relation c ̃ 4 d = - 8 π 2 c m between the response parameter (c ̃ 4 d) and the anomaly coefficient (c m ). This establishes a connection between the coefficients appearing in a first order and a third order derivative terms in the constitutive relation. © 2014 The Author(s).

Barba M.,Italian Agricultural Research Council | Czosnek H.,Hebrew University of Jerusalem | Hadidi A.,U.S. Department of Agriculture
Viruses | Year: 2014

Next-generation high throughput sequencing technologies became available at the onset of the 21st century. They provide a highly efficient, rapid, and low cost DNA sequencing platform beyond the reach of the standard and traditional DNA sequencing technologies developed in the late 1970s. They are continually improved to become faster, more efficient and cheaper. They have been used in many fields of biology since 2004. In 2009, next-generation sequencing (NGS) technologies began to be applied to several areas of plant virology including virus/viroid genome sequencing, discovery and detection, ecology and epidemiology, replication and transcription. Identification and characterization of known and unknown viruses and/or viroids in infected plants are currently among the most successful applications of these technologies. It is expected that NGS will play very significant roles in many research and non-research areas of plant virology. © 2013 by the authors; licensee MDPI, Basel, Switzerland.

Goldschmidt E.E.,Hebrew University of Jerusalem
Frontiers in Plant Science | Year: 2014

Grafting, an old plant propagation practice, is still widely used with fruit trees and in recent decades also with vegetables. Taxonomic proximity is a general prerequisite for successful graft-take and long-term survival of the grafted, composite plant. However, the mechanisms underlying interspecific graft incompatibility are as yet insufficiently understood. Hormonal signals, auxin in particular, are believed to play an important role in the wound healing and vascular regeneration within the graft union zone. Incomplete and convoluted vascular connections impede the vital upward and downward whole plant transfer routes. Long-distance protein, mRNA and small RNA graft-transmissible signals currently emerge as novel mechanisms which regulate nutritional and developmental root/top relations and may play a pivotal role in grafting physiology. Grafting also has significant pathogenic projections. On one hand, stock to scion mechanical contact enables the spread of diseases, even without a complete graft union. But, on the other hand, grafting onto resistant rootstocks serves as a principal tool in the management of fruit tree plagues and vegetable soil-borne diseases. The ‘graft hybrid’ historic controversy has not yet been resolved. Recent evidence suggests that epigenetic modification of DNA-methylation patterns may account for certain graft-transformation phenomena. Root grafting is a wide spread natural phenomenon; both intraspecific and interspecific root grafts have been recorded. Root grafts have an evolutionary role in the survival of storm-hit forest stands as well as in the spread of devastating diseases. A more fundamental evolutionary role is hinted by recent findings that demonstrate plastid and nuclear genome transfer between distinct Nicotiana species in the graft union zone, within a tissue culture system. This has led to the formation of alloploid cells that, under laboratory conditions, gave rise to a novel, alloploid Nicotiana species, indicating that natural grafts may play a role in plant speciation, under certain circumstances. © 2014 Goldschmidt.

Piran T.,Hebrew University of Jerusalem | Jimenez R.,University of Barcelona | Jimenez R.,Harvard University
Physical Review Letters | Year: 2014

As a copious source of gamma rays, a nearby galactic gamma ray burst (GRB) can be a threat to life. Using recent determinations of the rate of GRBs, their luminosity function, and properties of their host galaxies, we estimate the probability that a life-threatening (lethal) GRB would take place. Amongst the different kinds of GRBs, long ones are most dangerous. There is a very good chance (but no certainty) that at least one lethal GRB took place during the past 5 gigayears close enough to Earth as to significantly damage life. There is a 50% chance that such a lethal GRB took place during the last 500×106years, causing one of the major mass extinction events. Assuming that a similar level of radiation would be lethal to life on other exoplanets hosting life, we explore the potential effects of GRBs to life elsewhere in the Galaxy and the Universe. We find that the probability of a lethal GRB is much larger in the inner Milky Way (95% within a radius of 4 kpc from the galactic center), making it inhospitable to life. Only at the outskirts of the Milky Way, at more than 10 kpc from the galactic center, does this probability drop below 50%. When considering the Universe as a whole, the safest environments for life (similar to the one on Earth) are the lowest density regions in the outskirts of large galaxies, and life can exist in only ≈10% of galaxies. Remarkably, a cosmological constant is essential for such systems to exist. Furthermore, because of both the higher GRB rate and galaxies being smaller, life as it exists on Earth could not take place at z>0.5. Early life forms must have been much more resilient to radiation. © 2014 American Physical Society.

Zamir D.,Hebrew University of Jerusalem
PLoS Biology | Year: 2013

In crop genetics and breeding research, phenotypic data are collected for each plant genotype, often in multiple locations and field conditions, in search of the genomic regions that confer improved traits. But what is happening to all of these phenotypic data? Currently, virtually none of the data generated from the hundreds of phenotypic studies conducted each year are being made publically available as raw data; thus there is little we can learn from past experience when making decisions about how to breed better crops for the future. This ongoing loss of phenotypic information, particularly about crop productivity, must be stopped if we are to meet the considerable challenge of increasing food production sufficiently to meet the needs of a growing world population. Here I present a road map for developing and implementing an information network to share data on crop plant phenotypes. © 2013 Dani Zamir.

London N.,University of California at San Francisco | Raveh B.,University of California at San Francisco | Schueler-Furman O.,Hebrew University of Jerusalem
Current Opinion in Structural Biology | Year: 2013

Peptide-mediated interactions are gaining increased attention due to their predominant roles in the many regulatory processes that involve dynamic interactions between proteins. The structures of such interactions provide an excellent starting point for their characterization and manipulation, and can provide leads for targeted inhibitor design. The relatively few experimentally determined structures of peptide-protein complexes can be complemented with an outburst of modeling approaches that have been introduced in recent years, with increasing accuracy and applicability to ever more systems. We review different methods to address the considerable challenges in modeling the binding of a short yet highly flexible peptide to its partner. These methods apply an array of sampling strategies and draw from a recent amassing of knowledge about the biophysical nature of peptide-protein interactions. We elaborate on applications of these structure-based approaches and in particular on the characterization of peptide binding specificity to different peptide-binding domains and enzymes. Such applications can identify new biological targets and thus complement our current view of protein-protein interactions in living organisms. Accurate peptide-protein docking is of particular importance in the light of increased appreciation of the crucial functional roles of disordered regions and the many linear binding motifs embedded within. © 2013 Elsevier Ltd.

Dillin A.,Howard Hughes Medical Institute | Cohen E.,Hebrew University of Jerusalem
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2011

Late onset is a common hallmark character of numerous disorders including human neurodegenerative maladies such as Huntington's, Parkinson's and Alzheimer's diseases. Why these diseases manifest in aged individuals and why distinct disorders share strikingly similar emergence patterns were until recently unsolved enigmas. During the past decade, invertebrate-based studies indicated that the insulin/IGF signalling pathway (IIS) mechanistically links neurodegenerative-associated toxic protein aggregation and ageing; yet, until recently it was unclear whether this link is conserved from invertebrates to mammals. Recent studies performed in Alzheimer's mouse models indicated that ageing alteration by IIS reduction slows the progression of Alzheimer's-like disease, protects the brain and mitigates the behavioural, pathological and biochemical impairments associated with the disease. Here, we review these novel studies and discuss the potential of ageing alteration as a therapeutic approach for the treatment of late onset neurodegeneration. © 2011 The Royal Society.

Flashner-Abramson E.,Hebrew University of Jerusalem
Oncogene | Year: 2015

It is well known that specific signal transduction inhibitors rarely suffice as anti-cancer agents. In most cases, tumors possess primary drug resistance due to their inherent heterogeneity, or acquire drug resistance due to genomic instability and acquisition of mutations. Here we expand our previous study of the novel compound, NT157, and show that it acts as a dual-targeting agent that invokes the blockage of two signal transduction pathways that are central to the development and maintenance of multiple human cancers. We show that NT157 targets not only IGF1R-IRS1/2, as previously reported, but also the Stat3 signaling pathway and demonstrates remarkable anti-cancer characteristics in A375 human melanoma cells and in a metastatic melanoma model in mice.Oncogene advance online publication, 29 June 2015; doi:10.1038/onc.2015.229. © 2015 Macmillan Publishers Limited

Bergan J.F.,Howard Hughes Medical Institute | Ben-Shaul Y.,Hebrew University of Jerusalem | Dulac C.,Howard Hughes Medical Institute
eLife | Year: 2014

Animal-animal recognition within, and across species, is essential for predator avoidance and social interactions. Despite its essential role in orchestrating responses to animal cues, basic principles of information processing by the vomeronasal system are still unknown. The medial amygdala (MeA) occupies a central position in the vomeronasal pathway, upstream of hypothalamic centers dedicated to defensive and social responses. We have characterized sensory responses in the mouse MeA and uncovered emergent properties that shed new light onto the transformation of vomeronasal information into sex- and species-specific responses. In particular, we show that the MeA displays a degree of stimulus selectivity and a striking sexually dimorphic sensory representation that are not observed in the upstream relay of the accessory olfactory bulb (AOB). Furthermore, our results demonstrate that the development of sexually dimorphic circuits in the MeA requires steroid signaling near the time of puberty to organize the functional representation of sensory stimuli.

Cabantchik Z.I.,Hebrew University of Jerusalem
Frontiers in Pharmacology | Year: 2014

In living systems iron appears predominantly associated with proteins, but can also be detected in forms referred as labile iron, which denotes the combined redox properties of iron and its amenability to exchange between ligands, including chelators. The labile cell iron (LCI) composition varies with metal concentration and substances with chelating groups but also with pH and the medium redox potential. Although physiologically in the lower μM range, LCI plays a key role in cell iron economy as cross-roads of metabolic pathways. LCI levels are continually regulated by an iron-responsive machinery that balances iron uptake versus deposition into ferritin. However, LCI rises aberrantly in some cell types due to faulty cell utilization pathways or infiltration by pathological iron forms that are found in hemosiderotic plasma. As LCI attains pathological levels, it can catalyze reactive O species (ROS) formation that, at particular threshold, can surpass cellular anti-oxidant capacities and seriously damage its constituents. While in normal plasma and interstitial fluids, virtually all iron is securely carried by circulating transferrin (Tf; that renders iron essentially non-labile), in systemic iron overload (IO), the total plasma iron binding capacity is often surpassed by a massive iron influx from hyperabsorptive gut or from erythrocyte overburdened spleen and/or liver. As plasma Tf approaches iron saturation, labile plasma iron (LPI) emerges in forms that can infiltrate cells by unregulated routes and raise LCI to toxic levels. Despite the limited knowledge available on LPI speciation in different types and degrees of IO, LPI measurements can be and are in fact used for identifying systemic IO and for initiating/adjusting chelation regimens to attain full-day LPI protection. A recent application of labile iron assay is the detection of labile components in intravenous iron formulations per se as well as in plasma (LPI) following parenteral iron administration. © 2014 Cabantchik.

Feitelson D.G.,Hebrew University of Jerusalem
Operating Systems Review (ACM) | Year: 2015

Being able to repeat experiments is considered a hallmark of the scientific method, used to confirm or refute hypotheses and previously obtained results. But this can take many forms, from precise repetition using the original experimental artifacts, to conceptual reproduction of the main experimental idea using new artifacts. Furthermore, the conclusions from previous work can also be corroborated using a different experimental methodology altogether. In order to promote a better understanding and use of such methodologies we propose precise definitions for different terms, and suggest when and why each should be used.

Oren A.,Hebrew University of Jerusalem
Frontiers in Microbiology | Year: 2013

Extremely halophilic microorganisms that accumulate KCl for osmotic balance (the Halobacteriaceae, Salinibacter) have a large excess of acidic amino acids in their proteins. This minireview explores the occurrence of acidic proteomes in halophiles of different physiology and phylogenetic affiliation. For fermentative bacteria of the order Halanaerobiales, known to accumulate KCl, an acidic proteome was predicted. However, this is not confirmed by genome analysis. The reported excess of acidic amino acids is due to a high content of Gln and Asn, which yield Glu and Asp upon acid hydrolysis. The closely related Halorhodospira halophila and Halorhodospira halochloris use different strategies to cope with high salt. The first has an acidic proteome and accumulates high KCl concentrations at high salt concentrations; the second does not accumulate KCl and lacks an acidic proteome. Acidic proteomes can be predicted from the genomes of some moderately halophilic aerobes that accumulate organic osmotic solutes (Halomonas elongata, Chromohalobacter salexigens) and some marine bacteria. Based on the information on cultured species it is possible to understand the pI profiles predicted from metagenomic data from hypersaline environments. © 2013 Oren.

Rappoport Z.,Hebrew University of Jerusalem
Israel Journal of Chemistry | Year: 2015

After finishing high school in Pinsk, Russia, Chaim Weizmann studied two semesters in the Technical University of Darmstadt, returned home for a year, and in 1895 registered as a chemistry student at the Charlottenburg Technical University at Berlin. He studied and worked in the research group of A. Bistrzycki on synthetic dyestuffs and received a patent in the field. He graduated after 3 years and followed Bistrzycki to Freiburg, Switzerland, where he received in January 1899 a Ph.D. degree with a grade of Magna cum laude. He became a Privatdocent at the University of Geneva, worked in Prof. C. Graebe's group, published papers and patents and sold patents. In 1904, he moved to the University of Manchester in the UK and collaborated with Prof. William Henry Perkin Jr. in research on synthetic dyestuffs and natural products, and started to work with him on the synthesis of acetone by fermentation. He failed to be nominated to Perkin's chair when Perkin left in 1913, but became a Reader and head of the biochemistry laboratory. After a conflict with Perkin, he continued alone with the acetone synthesis project, found a bacterium that fermented the starch of corn, potatoes, and chestnuts to acetone and butyl alcohol, which was more efficient than a bacterium found by Perkin and co-workers. The urgent need for acetone in World War One for military purpose and the high yield of his bacterium in acetone-producing fermentation, compared with the bacterium of his competitors, made Weizmann's process the favored one by the British military during the war. Weizmann scaled up acetone production and increased its yield by increasing the sophistication of the process by using a high degree of sterilization. For his contributions he is regarded as the father of industrial biotechnology. His contribution to the war effort opened the door to the British leadership in his Zionistic activity. However, this activity and his scientific activity at later periods are not covered in this article. © 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Shamir R.R.,Hebrew University of Jerusalem
Medical image computing and computer-assisted intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention | Year: 2010

We present a new preoperative planning method for reducing the risk associated with insertion of straight tools in image-guided keyhole neurosurgery. The method quantifies the risks of multiple candidate trajectories and presents them on the outer head surface to assist the neurosurgeon in selecting the safest path. The surgeon can then define and/or revise the trajectory, add a new one using interactive 3D visualization, and obtain a quantitative risk measures. The trajectory risk is evaluated based on the tool placement uncertainty, on the proximity of critical brain structures, and on a predefined table of quantitative geometric risk measures. Our results on five targets show a significant reduction in trajectory risk and a shortening of the preoperative planning time as compared to the current routine method.

This work examines the relations between the Cadomian-type peri-Gondwana blocks and West and North Africa and Arabia (WNA) and the sediments derived therefrom during the Neoproterozoic. This provides insights regarding the formation, development, and paleogeography of the Cadomian domain, and when interpreted in the framework of plate tectonic processes allows proposing an internally consistent, though tentative, picture of the Neoproterozoic history of the domain before the Cadomian orogeny. Since WNA is built of terranes that were originally dispersed over a ≥ 2000 km wide area (E-W), it was only when their assembly was well advanced (≤ ca. 680-650 Ma ago) that they formed a continuous continental area with a well-defined margin next to which a continuous peripheral Cadomian domain could be shaped. Most likely it formed by accretion of various elements to the newly formed WNA margin, which is supported by several lines of evidence. The exposed basement rocks of the Cadomian domain are usually ≤ 600-580 Ma old (Late Ediacaran and Early Paleozoic). Before the Cadomian orogeny much of the domain comprised marine basins, several hundred kilometers wide, filled mainly by thick siliciclastics associated with variable amounts of igneous rocks. A large fraction of the sediments was produced by extensive erosion of WNA, but the West African Craton probably had a secondary role as a sediment source. Subduction-related igneous rocks occur in basinal areas close to the northern active margin of the Cadomian domain, and these areas were affected by the Cadomian orogeny. There arc-derived, rather than WNA-derived detritus appears to be present, proving the existence of adjacent magmatic arcs, although the arcs are little exposed. As sediment transport was necessarily down-slope, the distribution of WNA- and arc-derived detritus and its termporal changes provide insights regarding the slopes of basin-floors and thus the paleogeography, while changes in their distribution most likely record tectonic activity. However, these issues still require further study. The Late Ediacaran paleogeographic setting recorded by the exposures is interpreted as comprising backarc basins and magmatic arcs, with igneous activity and deformation being more pronounced in the outboard parts of the domain (including basinal areas), similar to the situation in the Western Pacific. It is hypothesized that, as in the latter area, the entire system was controlled by retreat (roll back) of the bordering subduction zone, and that this setting was produced ca. 600 Ma ago or somewhat earlier by modification of a pre-existing active margin that was initially shaped by the accretion of the Cadomian domain to WNA. However, the absence of direct evidence about the early history of the domain does not allow interpretation beyond this general picture. © 2015 International Association for Gondwana Research.

Canello T.,Hebrew University of Jerusalem
PLoS pathogens | Year: 2010

While elucidating the peculiar epitope of the alpha-PrP mAb IPC2, we found that PrPSc exhibits the sulfoxidation of residue M213 as a covalent signature. Subsequent computational analysis predicted that the presence of sulfoxide groups at both Met residues 206 and 213 destabilize the alpha-fold, suggesting oxidation may facilitate the conversion of PrPC into PrPSc. To further study the effect of oxidation on prion formation, we generated pAbs to linear PrP peptides encompassing the Helix-3 region, as opposed to the non-linear complexed epitope of IPC2. We now show that pAbs, whose epitopes comprise Met residues, readily detected PrPC, but could not recognize most PrPSc bands unless they were vigorously reduced. Next, we showed that the alpha-Met pAbs did not recognize newly formed PrPSc, as is the case for the PK resistant PrP present in lines of prion infected cells. In addition, these reagents did not detect intermediate forms such as PK sensitive and partially aggregated PrPs present in infected brains. Finally, we show that PrP molecules harboring the pathogenic mutation E200K, which is linked to the most common form of familial CJD, may be spontaneously oxidized. We conclude that the oxidation of methionine residues in Helix-3 represents an early and important event in the conversion of PrPC to PrPSc. We believe that further investigation into the mechanism and role of PrP oxidation will be central in finally elucidating the mechanism by which a normal cell protein converts into a pathogenic entity that causes fatal brain degeneration.

Zhang X.-J.,CAS Shanghai Institutes for Biological Sciences | Greenberg D.S.,Hebrew University of Jerusalem
Frontiers in Molecular Neuroscience | Year: 2012

To date, more than 40 different types of cells from primary cultures or cell lines have shown AChE expression during apoptosis and after the induction apoptosis by different stimuli. It has been well-established that increased AChE expression or activity is detected in apoptotic cells after apoptotic stimuli in vitro and in vivo, and AChE could be therefore used as a marker of apoptosis. AChE is not an apoptosis initiator, but the cells in which AChE is overexpressed undergo apoptosis more easily than controls. Interestingly, cells with downregulated levels of AChE are not sensitive to apoptosis induction and AChE deficiency can protect against apoptosis. Some tumor cells do not express AChE, but when AChE is introduced into a tumor cell, the cells cease to proliferate and undergo apoptosis more readily. Therefore, AChE can be classified as a tumor suppressor gene. AChE plays a pivotal role in apoptosome formation, and silencing of the AChE gene prevents caspase-9 activation, with consequent decreased cell viability, nuclear condensation, and poly (adenosine diphosphate-ribose) polymerase cleavage. AChE is translocated into the nucleus, which may be an important event during apoptosis. Several questions still need to be addressed, and further studies that address the non-classical function of AChE in apoptosis are needed. © 2012 Zhang and Greenberg.

De Richter D.B.,Duke University | Yaalon D.H.,Hebrew University of Jerusalem
Soil Science Society of America Journal | Year: 2012

In 1961, the late Marlin G. Cline wrote a remarkable essay entitled, "The Changing Model of Soil" for the 25th Anniversary Issue of the Soil Science Society of America Proceedings. Cline was most impressed with how geomorphology was enriching pedology, and with the increasingly sophisticated views of soil time and of the processes of soil formation. We revisit Cline's general objectives by re-evaluating the changing model of soil from the perspective of the early 21st century, and by taking stock of the application of soil models to contemporary needs and challenges. Today, three ongoing changes in the genetic model of soil have far-reaching consequences for the future of soil science: (i) that soil is being transformed globally from natural to human-natural body, (ii) that the lower boundary of soil is much deeper than the solum historically confi ned to O to B horizons, and (iii) that most soils are a kind of pedogenic paleosol, archival products of soil-forming processes that have ranged widely over the life of most soils. Together and each in their own way, these three changes in the model of soil impact directly human-soil relations and give structure and guidance to the science of anthropedology. In other words, human forcings represent a global wave of soil polygenesis altering fluxes of matter and energy and transforming the thermodynamics of soils as potentially very deep systems. Anthropedogenesis needs much better quantifi cation to evaluate the future of soil and the wider environment. © Soil Science Society of America.

The origin of the lowest triplet states - locally excited or charge shifted (T LEvs. T CS) - is a key point in the discussion of the charge shift phenomena of 9-mesityl-10-methylacridinium (see Fukuzumi et al. Phys. Chem. Chem. Phys., 2008, 10, 5159 vs. Benniston et al., Phys. Chem. Chem. Phys., 2008, 10, 5156). Coordination of the anion on the mesityl moiety provides the effective stabilization of the charge-shifted state. © 2010 the Owner Societies.

Nelken I.,Hebrew University of Jerusalem
Frontiers in Human Neuroscience | Year: 2011

Sound processing by the auditory system is understood in unprecedented details, even compared with sensory coding in the visual system. Nevertheless, we do not understand yet the way in which some of the simplest perceptual properties of sounds are coded in neuronal activity. This poses serious difficulties for linking neuronal responses in the auditory system and music processing, since music operates on abstract representations of sounds. Paradoxically, although perceptual representations of sounds most probably occur high in auditory system or even beyond it, neuronal responses are strongly affected by the temporal organization of sound streams even in subcortical stations. Thus, to the extent that music is organized sound, it is the organization, rather than the sound, which is represented first in the auditory brain. © 2011 Nelken.

Fridlender Z.G.,Hebrew University of Jerusalem | Fridlender Z.G.,University of Pennsylvania | Albelda S.M.,University of Pennsylvania
Carcinogenesis | Year: 2012

Neutrophils play an established role in host defense and in killing invading microorganisms. Although neutrophils are traditionally considered in the context of their antibacterial functions, it is becoming increasingly clear that tumor-associated neutrophils (TAN) play a major role in cancer biology. Neutrophils make up a significant portion of the inflammatory cell infiltrate in many models of cancer. Like all other leukocytes, they move into tissues under the influence of specific chemokines, cytokines and cell adhesion molecules. The tumor microenvironment has been shown to be responsible for their recruitment in cancer. We have found that TAN are a distinct population of neutrophils, differing markedly in their transcriptomic profile from both naive neutrophils and the granulocytic fraction of myeloid-derived suppressor cells. Studies have demonstrated specific examples of tumor-mediated signals (such as transforming growth factor-β) that induce the formation of a pro-tumorigenic (N2) phenotype capable of supporting tumor growth and suppressing the antitumor immune response. However, there are also studies showing that TAN can also have an antitumorigenic (N1) phenotype. Herein, we explore the literature on the different mechanisms of TAN recruitment to tumors, the unique characteristics of TAN and what shapes their pro- and/or antitumor effects. © The Author 2012. Published by Oxford University Press. All rights reserved.

Bar-Joseph Z.,Carnegie Mellon University | Gitter A.,Carnegie Mellon University | Simon I.,Hebrew University of Jerusalem
Nature Reviews Genetics | Year: 2012

Biological processes are often dynamic, thus researchers must monitor their activity at multiple time points. The most abundant source of information regarding such dynamic activity is time-series gene expression data. These data are used to identify the complete set of activated genes in a biological process, to infer their rates of change, their order and their causal effects and to model dynamic systems in the cell. In this Review we discuss the basic patterns that have been observed in time-series experiments, how these patterns are combined to form expression programs, and the computational analysis, visualization and integration of these data to infer models of dynamic biological systems. © 2012 Macmillan Publishers Limited. All rights reserved.

Even-Zohar C.,Hebrew University of Jerusalem
Combinatorics Probability and Computing | Year: 2012

Let A and B be two affinely generating sets of ℤ2 n. As usual, we denote their Minkowski sum by A+B. How small can A+B be, given the cardinalities of A and B? We give a tight answer to this question. Our bound is attained when both A and B are unions of cosets of a certain subgroup of ℤ2 n. These cosets are arranged as Hamming balls, the smaller of which has radius 1. By similar methods, we re-prove the Freimana-Ruzsa theorem in ℤ2 n, with an optimal upper bound. Denote by F(K) the maximal spanning constant |A|/|A| over all subsets A ⊆ ℤ2 n with doubling constant |A+A|/|A| ≤K. We explicitly calculate F(K), and in particular show that 4K/4K ≤ F(K)•(1+o(1)) ≤ 4K/2K. This improves the estimate F(K) = poly(K)4K, found recently by Green and Tao [17] and by Konyagin [23]. © 2012 Cambridge University Press.

Barenholz Y.,Hebrew University of Jerusalem
Journal of Controlled Release | Year: 2012

Doxil®, the first FDA-approved nano-drug (1995), is based on three unrelated principles: (i) prolonged drug circulation time and avoidance of the RES due to the use of PEGylated nano-liposomes; (ii) high and stable remote loading of doxorubicin driven by a transmembrane ammonium sulfate gradient, which also allows for drug release at the tumor; and (iii) having the liposome lipid bilayer in a liquid ordered phase composed of the high-T m (53°C) phosphatidylcholine, and cholesterol. Due to the EPR effect, Doxil is passively targeted to tumors and its doxorubicin is released and becomes available to tumor cells by as yet unknown means. This review summarizes historical and scientific perspectives of Doxil development and lessons learned from its development and 20 years of its use. It demonstrates the obligatory need for applying an understanding of the cross talk between physicochemical, nano-technological, and biological principles. However, in spite of the large reward, ~ 2 years after Doxil-related patents expired, there is still no FDA-approved generic Doxil available. © 2012 Elsevier B.V.

Werner S.,Hebrew University of Jerusalem
Psychiatry Research | Year: 2012

Hope, as a basic resource in human life, may affect individuals' perceptions of subjective well-being (SWB). Further, understanding individuals' needs is essential to improving their SWB. It is unclear how the impact of hope on SWB may be mediated by needs. The current study aimed to examine a mediation model for the relation between hope and SWB among individuals with serious mental illness (SMI). Face-to-face structured interviews were conducted with 172 individuals with SMI. Instruments included the Personal Wellbeing Index, the Hope Scale, and the Camberwell Assessment of Needs. Hope and needs were predictive of 40% of the variability in SWB, with hope being a stronger predictor. Having no needs was positively predictive of SWB, while total number of needs was negatively predictive of SWB. Path analyses revealed a strong direct effect of hope on SWB and a weaker, though still strong, indirect effect mediated through needs. The results underscore the importance of hope in improving SWB and, consequently, enhancing the recovery process of individuals with SMI. Therefore, mental health services should focus on hope-building. © 2012 Elsevier Ltd.

Abramson J.H.,Hebrew University of Jerusalem
Epidemiologic Perspectives and Innovations | Year: 2011

Background. The WINPEPI computer programs for epidemiologists are designed for use in practice and research in the health field and as learning or teaching aids. The programs are free, and can be downloaded from the Internet. Numerous additions have been made in recent years. Implementation. There are now seven WINPEPI programs: DESCRIBE, for use in descriptive epidemiology; COMPARE2, for use in comparisons of two independent groups or samples; PAIRSetc, for use in comparisons of paired and other matched observations; LOGISTIC, for logistic regression analysis; POISSON, for Poisson regression analysis; WHATIS, a "ready reckoner" utility program; and ETCETERA, for miscellaneous other procedures. The programs now contain 122 modules, each of which provides a number, sometimes a large number, of statistical procedures. The programs are accompanied by a Finder that indicates which modules are appropriate for different purposes. The manuals explain the uses, limitations and applicability of the procedures, and furnish formulae and references. Conclusions. WINPEPI is a handy resource for a wide variety of statistical routines used by epidemiologists. Because of its ready availability, portability, ease of use, and versatility, WINPEPI has a considerable potential as a learning and teaching aid, both with respect to practical procedures in the planning and analysis of epidemiological studies, and with respect to important epidemiological concepts. It can also be used as an aid in the teaching of general basic statistics. © 2011 Abramson; licensee BioMed Central Ltd.

Wiseman H.,Haifa University | Tishby O.,Hebrew University of Jerusalem
Psychotherapy Research | Year: 2014

Objective: We examined the associations between client attachment, client attachment to the therapist, and symptom change, as well as the effects of client-therapist attachment match on outcome. Clients (n = 67) and their therapists (n = 27) completed the ECR to assess attachment. Method: Clients completed also the Client Attachment to Therapist scale three times (early, middle, and late sessions) and the OQ-45 at intake and four times over the course of a year of psychodynamic psychotherapy. Results: Clients characterized by avoidant attachment and by avoidant attachment to their therapist showed the least improvement. A low-avoidant client-therapist attachment match led to a greater decrease in symptom distress than when a low-avoidant therapist treated a high-avoidant client. Conclusions: These findings suggest the importance of considering client-therapist attachment matching and the need to pay attention to the special challenges involved in treating avoidant clients in order to facilitate progress in psychotherapy. © 2014 © 2014 Society for Psychotherapy Research.

Fridman Y.,Technion - Israel Institute of Technology | Elkouby L.,Technion - Israel Institute of Technology | Holland N.,Technion - Israel Institute of Technology | Vragovic K.,Technion - Israel Institute of Technology | And 2 more authors.
Genes and Development | Year: 2014

Coherent plant growth requires spatial integration of hormonal pathways and cell wall remodeling activities. However, the mechanisms governing sensitivity to hormones and how cell wall structure integrates with hormonal effects are poorly understood. We found that coordination between two types of epidermal root cells, hair and nonhair cells, establishes root sensitivity to the plant hormones brassinosteroids (BRs). While expression of the BR receptor BRASSINOSTEROID-INSENSITIVE1 (BRI1) in hair cells promotes cell elongation in all tissues, its high relative expression in nonhair cells is inhibitory. Elevated ethylene and deposition of crystalline cellulose underlie the inhibitory effect of BRI1. We propose that the relative spatial distribution of BRI1, and not its absolute level, fine-tunes growth. © 2014 Fridman et al.

London N.,Institute for Medical Research IMRIC | Movshovitz-Attias D.,Hebrew University of Jerusalem | Schueler-Furman O.,Institute for Medical Research IMRIC
Structure | Year: 2010

Peptide-protein interactions are very prevalent, mediating key processes such as signal transduction and protein trafficking. How can peptides overcome the entropic cost involved in switching from an unstructured, flexible peptide to a rigid, well-defined bound structure? A structure-based analysis of peptide-protein interactions unravels that most peptides do not induce conformational changes on their partner upon binding, thus minimizing the entropic cost of binding. Furthermore, peptides display interfaces that are better packed than protein-protein interfaces and contain significantly more hydrogen bonds, mainly those involving the peptide backbone. Additionally, "hot spot" residues contribute most of the binding energy. Finally, peptides tend to bind in the largest pockets available on the protein surface. Our study is based on peptiDB, a new and comprehensive data set of 103 high-resolution peptide-protein complex structures. In addition to improved understanding of peptide-protein interactions, our findings have direct implications for the structural modeling, design, and manipulation of these interactions. © 2010 Elsevier Ltd. All rights reserved.

Mosheiov G.,Hebrew University of Jerusalem | Oron D.,University of Sydney
Computers and Operations Research | Year: 2012

In various real life scheduling systems job processing times vary according to the number of jobs previously processed. The vast majority of studies assume a restrictive functional form to describe job processing times. In this note, we address a scheduling problem with the most general job processing time functions. The machine setting assumed is an m-machine proportionate flowshop, and the objective function is minimum number of tardy jobs. We show that the problem can be formulated as a bottleneck assignment problem with a maximum cardinality constraint. An efficient polynomial time (O(n4 log n)) solution is introduced. © 2011 Published by Elsevier Ltd. All rights reserved.

Helman A.,Hebrew University of Jerusalem
Nature Medicine | Year: 2016

Cellular senescence is thought to contribute to age-associated deterioration of tissue physiology. The senescence effector p16Ink4a is expressed in pancreatic beta cells during aging and limits their proliferative potential; however, its effects on beta cell function are poorly characterized. We found that beta cell–specific activation of p16Ink4a in transgenic mice enhances glucose-stimulated insulin secretion (GSIS). In mice with diabetes, this leads to improved glucose homeostasis, providing an unexpected functional benefit. Expression of p16Ink4a in beta cells induces hallmarks of senescence—including cell enlargement, and greater glucose uptake and mitochondrial activity—which promote increased insulin secretion. GSIS increases during the normal aging of mice and is driven by elevated p16Ink4a activity. We found that islets from human adults contain p16Ink4a-expressing senescent beta cells and that senescence induced by p16Ink4a in a human beta cell line increases insulin secretion in a manner dependent, in part, on the activity of the mechanistic target of rapamycin (mTOR) and the peroxisome proliferator-activated receptor (PPAR)-γ proteins. Our findings reveal a novel role for p16Ink4a and cellular senescence in promoting insulin secretion by beta cells and in regulating normal functional tissue maturation with age. © 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.

Pacher P.,U.S. National Institutes of Health | Mechoulam R.,Hebrew University of Jerusalem
Progress in Lipid Research | Year: 2011

The mammalian body has a highly developed immune system which guards against continuous invading protein attacks and aims at preventing, attenuating or repairing the inflicted damage. It is conceivable that through evolution analogous biological protective systems have been evolved against non-protein attacks. There is emerging evidence that lipid endocannabinoid signaling through cannabinoid 2 (CB 2) receptors may represent an example/part of such a protective system/armamentarium. Inflammation/tissue injury triggers rapid elevations in local endocannabinoid levels, which in turn regulate signaling responses in immune and other cells modulating their critical functions. Changes in endocannabinoid levels and/or CB 2 receptor expressions have been reported in almost all diseases affecting humans, ranging from cardiovascular, gastrointestinal, liver, kidney, neurodegenerative, psychiatric, bone, skin, autoimmune, lung disorders to pain and cancer, and modulating CB 2 receptor activity holds tremendous therapeutic potential in these pathologies. While CB 2 receptor activation in general mediates immunosuppressive effects, which limit inflammation and associated tissue injury in large number of pathological conditions, in some disease states activation of the CB 2 receptor may enhance or even trigger tissue damage, which will also be discussed alongside the protective actions of the CB 2 receptor stimulation with endocannabinoids or synthetic agonists, and the possible biological mechanisms involved in these effects. © 2010 Elsevier Ltd. All rights reserved.

Yirmiya R.,Hebrew University of Jerusalem
Current Osteoporosis Reports | Year: 2010

An increasing number of studies suggest an association between depression and osteoporosis. In a mouse model, depression induces bone loss, mediated by brain-to-bone sympathetic signaling. Depression and bone antianabolic sympathetic tone are alleviated by increasing central serotonin (5-hydroxytryptamine, 5-HT) levels. However, selective serotonin reuptake inhibitors (SSRIs), the first-line antidepressants, increase extracellular 5-HT levels but have deleterious skeletal effects. The skeletal serotonergic system consists of 5-HT receptors and the 5-HT transporter (5-HTT) in osteoblasts and osteocytes. 5-HTT is a transmembrane protein targeted by SSRIs. 5-HT restrains osteoblastic activity, thus leading to bone loss. Apparently, the negative skeletal effects of the peripheral SSRI-induced increase in 5-HT outweighs the skeletal benefits resulting from the enhanced central 5-HT antidepressant and antisympathetic activity. Overall, major depression appears as an important risk factor for osteoporosis. However, antidepressants, mainly SSRIs, should be evaluated in view of the causal relationship between depression and bone loss, and vis-à-vis their skeletal adverse effects. Patients with depressive disorders should undergo a routine skeletal evaluation and receive timely antiosteoporotic therapy, especially when SSRI treatment is prescribed. © 2010 Springer Science+Business Media, LLC.

Marcus Y.,Hebrew University of Jerusalem
Pure and Applied Chemistry | Year: 2013

Extraction reactions are identified, in which the main step is the replacement of the water that hydrates the ions in the aqueous phase by a solvation shell provided by the water-immiscible solvent. The change in solvation is measured by the standard molar Gibbs free energy of trans fer of the ion, which is related in a definite manner to certain properties of the solvent and of the ion and to the composition of the solvent, if it contains much water. Enthalpy or entropy changes may predominately control the transfer. These concepts are illustrated by the extraction of the halide anions into substituted phenols, of lithium, magnesium, and aluminium halides into (hydrous) 1-hexanol, and of dioxouranium (VI) and thorium or plutonium (IV) nitrates into neutral phosphoryl-group-containing solvents. © 2013, Walter de Gruyter. All rights reserved.

Meinhold G.,University of Gottingen | Morton A.C.,University of Cambridge | Morton A.C.,HM Research Associates | Avigad D.,Hebrew University of Jerusalem
Gondwana Research | Year: 2013

We present a synopsis of detrital zircon U-Pb ages of sandstones from North Africa and neighboring Israel and Jordan, which allows us to identify zones with characteristic sediment provenance along the northern Gondwana margin (in present-day coordinates) in Cambrian-Ordovician times, and helps us to unravel the peri-Gondwana jigsaw puzzle. A special feature of the early Paleozoic cover sequence of North Africa is the eastward increase of 1.1-0.95. Ga detrital zircons, which become ubiquitous in the early Paleozoic sandstones of the Saharan Metacraton. Detrital zircons aged about 2.7-2.5, 2.15-1.75 and 0.75-0.53. Ga are also present. Early Paleozoic sandstones with similar provenance are known from peri-Gondwana terranes in the Eastern and Western Mediterranean and from NW Iberia. These terranes need not be transported from western Gondwana (Amazonia) as suggested previously. They were likely located to the north of the Saharan Metacraton during the early Paleozoic before they rifted off from Gondwana. Furthermore, we recognize an increase, as stratigraphic ages get younger, of ca. 1.0. Ga detrital zircons at some point between the Late Cambrian and late Middle Ordovician. We speculate that this might be linked to far-field tectonics and regional uplift in central Gondwana related to plate-tectonic reorganization along the Gondwana margin, leading to erosion of ca. 1.0. Ga basement and country rocks of the Transgondwanan supermountain and fluvial dispersal of detritus toward the Gondwana margin. © 2012 International Association for Gondwana Research.

Litwin H.,Hebrew University of Jerusalem
International Psychogeriatrics | Year: 2011

Background: Although social network relationships are linked to mental health in late life, it is still unclear whether it is the structure of social networks or their perceived quality that matters. Methods: The current study regressed a dichotomous 8-item version of the Center for Epidemiological Studies Depression Scale (CESD-8) score on measures of social network relationships among Americans, aged 65-85 years, from the first wave of the National Social Life, Health and Aging Project. The network indicators included a structural variable - social network type - and a series of relationship quality indicators: perceived positive and negative ties with family, friends and spouse/ partner. Multivariate logistic regression analyses controlled for age, gender, education, income, race/ethnicity, religious affiliation, functional health and physical health. Results: The perceived social network quality variables were unrelated to the presence of a high level of depressive symptoms, but social network type maintained an association with this mental health outcome even after controlling for confounders. Respondents embedded in resourceful social network types in terms of social capital - "diverse," "friend" and "congregant" networks - reported less presence of depressive symptoms, to varying degrees. Conclusions: The results show that the structure of the network seems to matter more than the perceived quality of the ties as an indicator of depressive symptoms. Moreover, the composite network type variable stands out in capturing the differences in mental state. The construct of network type should be incorporated in mental health screening among older people who reside in the community. One's social network type can be an important initial indicator that one is at risk. © International Psychogeriatric Association 2011.

Hellman A.,Hebrew University of Jerusalem | Chess A.,Harvard University | Chess A.,Cambridge Broad Institute
Epigenetics and Chromatin | Year: 2010

Background. Epigenetic polymorphisms are a potential source of human diversity, but their frequency and relationship to genetic polymorphisms are unclear. DNA methylation, an epigenetic mark that is a covalent modification of the DNA itself, plays an important role in the regulation of gene expression. Most studies of DNA methylation in mammalian cells have focused on CpG methylation present in CpG islands (areas of concentrated CpGs often found near promoters), but there are also interesting patterns of CpG methylation found outside of CpG islands. Results. We compared DNA methylation patterns on both alleles between many pairs (and larger groups) of related and unrelated individuals. Direct observation and simulation experiments revealed that around 10% of common single nucleotide polymorphisms (SNPs) reside in regions with differences in the propensity for local DNA methylation between the two alleles. We further showed that for the most common form of SNP, a polymorphism at a CpG dinucleotide, the presence of the CpG at the SNP positively affected local DNA methylation in cis. Conclusions. Taken together with the known effect of DNA methylation on mutation rate, our results suggest an interesting interdependence between genetics and epigenetics underlying diversity in the human genome. © 2010 Hellman and Chess; licensee BioMed Central Ltd.

Ben-Arieh A.,Hebrew University of Jerusalem
Child Abuse and Neglect | Year: 2015

This study expands research on the relationship between community (defined here as a locality) characteristics and child maltreatment. Research in this field is not new, but it is scarce. Our study is unique by examining changes between two periods rather than focusing on one point in time. Furthermore, our study examines structural conditions in small and medium size localities in Israel, a non-Western and non-Christian society. We compare our results with those from studies on inner-city and suburban neighborhoods in Western countries and earlier studies in Israel. We collected data on 169 Israeli localities, ranging from small ones (with as few as 1,500 residents) to medium size localities (i.e., towns) (with as many as 50,000 residents) in which approximately 34% of the Israeli child population resides. Our study tested four hypotheses: (1) Socioeconomic characteristics of the locality will be negatively correlated with the availability of social services; (2) Reported child maltreatment rates will be negatively correlated with the socioeconomic characteristics of the locality; (3) The availability of social services will be positively correlated with reported child maltreatment rates; and (4) Overall reported child maltreatment rates will be negatively correlated with the overall status of the localities. We have supported our second and third hypothesis in full, and partially supported our first and fourth hypothesis. In particular we have demonstrated that while demographics play a different role in Israel than in other countries in regard to child maltreatment, social, economic and cultural context are crucial for understating reported rates of child maltreatment. © 2014 Elsevier Ltd.

Bialer M.,Hebrew University of Jerusalem | Midha K.K.,University of Saskatchewan
Epilepsia | Year: 2010

Most antiepileptic drugs (AEDs) are currently available as generic products, yet neurologists and patients are reluctant to switch to generics. Generic AEDs are regarded as bioequivalent to brand AEDs after meeting the average bioequivalence criteria; consequently, they are considered to be interchangeable with their respective brands without loss of efficacy and safety. According to the U.S. Food and Drug Administration (FDA) the present bioequivalence requirements are already so rigorous and constrained that there is little possibility that generics that meet regulatory bioequivalence criteria could lead to therapeutic problems. So is there a scientific rationale for the concerns about switching patients with epilepsy to bioequivalent generics? Herein we discuss the assessment of bioequivalence and propose a scaled-average bioequivalence approach where scaling of bioequivalence is carried out based on brand lot-to-lot variance as an alternative to the conventional bioequivalence test as a means to determine whether switching patients to generic formulations, or vice versa, is a safe and effective therapeutic option. Meeting the proposed scaled-average bioequivalence requirements will ensure that when an individual patient is switched, he or she has fluctuations in plasma levels similar to those from lot-to-lot of the brand reference levels and thus should make these generic products safely switchable without change in efficacy and safety outcomes. © 2010 International League Against Epilepsy.

Rosenmann H.,Hebrew University of Jerusalem
Current Alzheimer Research | Year: 2013

The drawbacks of amyloid immunotherapy, including the development of encephalitis, the lack of clinical improvement and of any effect on neurofibrillary tangles (NFTs), coupled with the central role of NFTs in dementia, may point that clearance of amyloid pathology is not sufficient for improving the dementia symptoms in Alzheimer's disease (AD) patients. This further supported the concept that immunotherapy targeting the NFT proteinous aggregates may be preferential. Yet, the encephalitogenicity of full-length tau protein under a proinflammatory CNS milieu, reported by us in immunized mice, demands to carefully and selectively target pathological tau, while not the normal functional tau, and assuring both efficacy (anti-NFT effect) as well as safety (free of encephalitis) of a potential vaccine. Accumulating evidence from animal studies shows that tau-immunotherapy, targeting selectively pathological tau, particularly the phosphorylated- tau isoforms, reduces the tau-pathology and improves the symptoms of dementia. These findings are based on studies from different research groups, including our laboratory, conducted in different animal models and using various immunization protocols. There is also evidence that the decrease in NFTs is antibody-mediated involving the endosomal/ lysosomal pathway. No adverse effects were reported by the research groups, including also our study in which mice were immunized with a single injection of phosphorylated-tau peptide under a CNS proinflammatory milieu. In this review, I discuss the studies reported in this field, focusing on different approaches, different immunization protocols and mechanistic aspects, with a focus on the promising efficacy of the tau-immunotherapy, while addressing the safety issues already in the preclinical stage, before progressing to clinical trials. © 2013 Bentham Science Publishers.

Oren A.,Hebrew University of Jerusalem
Journal of Biological Research (Greece) | Year: 2014

Halophilic representatives of the genus Dunaliella, notably D. salina and D. viridis, are found worldwide in salt lakes and saltern evaporation and crystallizer ponds at salt concentrations up to NaCl saturation. Thanks to the biotechnological exploitation of D. salina for β-carotene production we have a profound knowledge of the physiology and biochemistry of the alga. However, relatively little is known about the ecology of the members of the genus Dunaliella in hypersaline environments, in spite of the fact that Dunaliella is often the main or even the sole primary producer present, so that the entire ecosystem depends on carbon fixed by this alga. This review paper summarizes our knowledge about the occurrence and the activities of different Dunaliella species in natural salt lakes (Great Salt Lake, the Dead Sea and others), in saltern ponds and in other salty habitats where members of the genus have been found. © 2014 Oren; licensee BioMed Central.

Simons Y.B.,Hebrew University of Jerusalem | Turchin M.C.,University of Chicago | Pritchard J.K.,University of Chicago | Pritchard J.K.,Stanford University | And 2 more authors.
Nature Genetics | Year: 2014

Human populations have undergone major changes in population size in the past 100,000 years, including recent rapid growth. How these demographic events have affected the burden of deleterious mutations in individuals and the frequencies of disease mutations in populations remains unclear. We use population genetic models to show that recent human demography has probably had little impact on the average burden of deleterious mutations. This prediction is supported by two exome sequence data sets showing that individuals of west African and European ancestry carry very similar burdens of damaging mutations. We further show that for many diseases, rare alleles are unlikely to contribute a large fraction of the heritable variation, and therefore the impact of recent growth is likely to be modest. However, for those diseases that have a direct impact on fitness, strongly deleterious rare mutations probably do have an important role, and recent growth will have increased their impact. © 2014 Nature America, Inc. © 2014 Nature America, Inc.

Liverts E.Z.,Hebrew University of Jerusalem
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2014

The two-electron Schrödinger equation at the two-particle coalescences was studied for atomic three-body systems in S states. The general differential equation in three variables was reduced to the centrally symmetric field problem for the case of electron-nucleus and electron-electron coalescence lines. Specific potentials describing attractive and repulsive interactions between the coalesced pair of the electron and nucleus and the two coalesced electrons, respectively, were derived and studied. Interesting features of these potentials in the vicinity of the triple-coalescence point were found. The ground states of the helium atom, the negative ion of hydrogen, and the positive ion of lithium were explored as the typical examples of the helium isoelectronic sequence. © 2014 American Physical Society.

Ben-David Kolikant Y.,Hebrew University of Jerusalem
Computers and Education | Year: 2012

Today's students are often portrayed in the literature as enthusiastic and wholehearted users of the Internet for school purposes, in contrast with today's schools, in which the situation is of high ICT access and low use. Via interviews with 25 post-primary students, this study examined student attitudes toward using the Internet for school purposes, revealing the reasoning behind patterns of after school ICT use and underlying perceptions of learning, the teacher's role and the desired role of ICT in schooling. Students were revealed to be ambivalent: they considered the Internet to be easy to use, reducing workload and "fun", but at the same time "unreliable", not "serious" enough, and not containing what they "need to know". Thus, they primarily used it for "unimportant" assignments such as routine homework. Students described their learning goal as getting required "material" into their heads and saw the teachers as an (almost) exclusive authority regarding this required body of information, in line with schooling's information-focused agenda and teacher-centered practices. They were also less than enthusiastic about the integration of ICT into their curriculum. Although there is no apparent disconnect between school and students, it is argued that school should change in order to capitalize on the affordances of ICT and to better prepare students for life in the knowledge age. © 2012 Elsevier Ltd. All rights reserved.

Weiss I.D.,Hadassah University Hospital | Jacobson O.,Hebrew University of Jerusalem
Theranostics | Year: 2013

CXCR4 was found to be expressed by many different types of human cancers and its expression has been correlated with tumor aggressiveness, poor prognosis and resistance to chemotherapy. CXCR4 was also shown to contribute to metastatic seeding of organs that express its ligand CXCL12 and support the survival of these cells. These findings suggest that CXCR4 is a potentially attractive therapeutic target, and several antagonists and antibodies for this receptor were developed and are under clinical evaluation. Quantifying CXCR4 expression non-invasively might aid in prognostication as a mean for personalized therapy and post treatment monitoring. Multiple attempts were done over the recent years to develop imaging agents for CXCR4 using different technologies including PET, SPECT, fluorescent and bioluminescence, and will be reviewed in this paper. © Ivyspring International Publisher.

Ekstein D.,Hebrew University of Jerusalem
Epilepsy and Behavior | Year: 2015

Botanicals are increasingly used by people with epilepsy worldwide. However, despite abundant preclinical data on the anticonvulsant properties of many herbal remedies, there are very few human studies assessing safety and efficacy of these products in epilepsy. Additionally, the methodology of most of these studies only marginally meets the requirements of evidence-based medicine. Although the currently available evidence for the use of cannabinoids in epilepsy is similarly lacking, several carefully designed and well controlled industry-sponsored clinical trials of cannabis derivatives are planned to be completed in the next couple of years, providing the needed reliable data for the use of these products. The choice of the best botanical candidates with anticonvulsant properties and their assessment in well-designed clinical trials may significantly improve our ability to effectively and safely treat patients with epilepsy. This article is part of a Special Issue entitled "Botanicals for Epilepsy". © 2015 Elsevier Inc.

Ataria Candidate. Y.,Hebrew University of Jerusalem
Journal of Trauma and Dissociation | Year: 2014

Fundamental aspects of trauma-among them dissociation during trauma, which is considered one of the strongest predictors of posttraumatic stress disorder-are not fully understood. This article argues that the application of the phenomenological structure of time and the phenomenological description of the self (minimal self, sense of ownership, sense of agency, sense of self) to dissociation during trauma can improve our understanding of this phenomenon-at its occurrence and during any possible ensuing symptoms. In addition, it is argued that the phenomenological approach, as a method that focuses on the bodily level of experience, in particular the body as it is experienced from within, enables us to penetrate the traumatic experience. Thus, by applying the phenomenological approach we may be able to improve our understanding of the traumatic experience and enable the development of better treatment. Copyright © Taylor & Francis Group, LLC.

Shaik S.,Hebrew University of Jerusalem | Rzepa H.S.,Imperial College London | Hoffmann R.,Cornell University
Angewandte Chemie - International Edition | Year: 2013

What could be simpler than C2, a diatomic molecule that has the second strongest homonuclear bond? This molecule turns out to be a microcosm of the bonding issues that bother chemists, as is shown in this trialogue. Join the three authors in their lively debate, light a candle, as Faraday did, and see the excited states of C2! Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Jonathan T.,Hebrew University of Jerusalem
British Journal of Criminology | Year: 2010

Public attitudes towards the police are considered one of the important outcomes of policing in democratic countries. However, it is not clear how policing terrorism may affect these evaluations. The 'Rally Effect' provides a context for examining this question, and suggests that when faced with severe terrorism threats, public perceptions of the police will rise in the short term but decline over time. Utilizing this framework, this article examines fluctuations in attitudes of Jewish adults in Israel towards the police over the past decade, within the context of legitimacy and procedural justice. The results lend support for the hypothesized model, and suggest that in addition to police conduct, public attitudes toward the police may be influenced by larger social forces. © The Author 2009.

Brooks A.M.,University of Wisconsin - Madison | Kuhlen M.,University of California at Berkeley | Zolotov A.,Hebrew University of Jerusalem | Hooper D.,Fermi National Accelerator Laboratory
Astrophysical Journal | Year: 2013

It has been demonstrated that the inclusion of baryonic physics can alter the dark matter densities in the centers of low-mass galaxies, making the central dark matter slope more shallow than predicted in pure cold dark matter simulations. This flattening of the dark matter profile can occur in the most luminous subhalos around Milky Way mass galaxies. Zolotov et al. have suggested a correction to be applied to the central masses of dark matter-only satellites in order to mimic the affect of (1) the flattening of the dark matter cusp due to supernova feedback in luminous satellites and (2) enhanced tidal stripping due to the presence of a baryonic disk. In this paper, we apply this correction to the z = 0 subhalo masses from the high resolution, dark matter-only Via Lactea II (VL2) simulation, and find that the number of massive subhalos is dramatically reduced. After adopting a stellar mass to halo mass relationship for the VL2 halos, and identifying subhalos that are (1) likely to be destroyed by stripping and (2) likely to have star formation suppressed by photo-heating, we find that the number of massive, luminous satellites around a Milky Way mass galaxy is in agreement with the number of observed satellites around the Milky Way or M31. We conclude that baryonic processes have the potential to solve the missing satellites problem. © 2013. The American Astronomical Society. All rights reserved.

Ovadyahu Z.,Hebrew University of Jerusalem
Physical Review B - Condensed Matter and Materials Physics | Year: 2013

Transport measurements made on films of thallium-oxide (n-type semiconductor) are presented and discussed. The focus in this work is on the strongly-localized regime where charge transport is by variable-range hopping. It is demonstrated that, at liquid-helium temperatures, these films exhibit all the characteristic features of intrinsic electron glasses. These include a slow (logarithmic in time) conductance relaxation that may be induced by any of the following protocols: Quench cooling from high temperatures, sudden change of gate voltage, exposure to infrared radiation, and stressing the system with a non-Ohmic field. The microstructure of the films are characterized by electron microscopy and their carrier concentration are measured by Hall effect. Field-effect experiments reveal a memory dip that has a width compatible with the carrier concentration of the system as compared with previously studied electron glasses. It is observed that the common ingredient in all the systems that exhibit electron-glass effects is high carrier concentration suggesting that their localized sites may be multioccupied even when deep into the insulating regime. That lightly-doped semiconductors do not show intrinsic electron-glass effects is consistent with this empirical observation. The connection between the memory dip and the Coulomb gap is discussed in light of these findings. © 2013 American Physical Society.

Goren-Inbar N.,Hebrew University of Jerusalem
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2011

The Acheulian presence in the Dead Sea Rift and its environs is characterized by the discontinuity of its cultural manifestations. Nevertheless, the long stratigraphic sequences of the Acheulian Technocomplex provide a unique opportunity for synergetic examination along a temporal trajectory. Hominin cognitive and cultural behaviour are studied at Gesher Benot Yaáqov through analyses of lithic, palaeontological and palaeobotanical assemblages, as well as the Early-Middle Pleistocene environment, ecology and climate. The study attempts to reconstruct reduction sequences of some major artefact groups at the site, which include raw material acquisition, production, technology, typology, usage and discard. Experimental archaeology illustrates artefact mobility on the palaeolandscape. Strategies of biomass-exploitation are studied in detail, with other aspects yielding additional information on hominin subsistence and adaptive responses to their environment. The cultural marker of fire and the spatial association of selected categories of finds are integrated in the general synthesis, allowing reconstruction of the cultural and cognitive realm of Acheulian hominins. The synthesis attempts to reassess the abilities, social structure, subsistence and adaptability to the changing environment of hominins in the Levantine Corridor. © 2011 The Royal Society.

Huang H.-W.,Hebrew University of Jerusalem
Communications in Mathematical Physics | Year: 2015

Since the introduction of Askey–Wilson algebras by Zhedanov in 1991, the classification of the finite-dimensional irreducible modules of Askey–Wilson algebras remains open. A universal analog $${\triangle_q}$$▵q of the Askey–Wilson algebras was recently studied. In this paper, we consider a family of infinite-dimensional $${\triangle_q}$$▵q-modules. By the universal property of these $${\triangle_q}$$▵q-modules, we classify the finite-dimensional irreducible $${\triangle_q}$$▵q-modules when q is not a root of unity. © 2015, Springer-Verlag Berlin Heidelberg.

Gal A.,Hebrew University of Jerusalem
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2015

The large charge symmetry breaking (CSB) implied by the Λ binding energy difference δBΛ4(0g.s.+)≡BΛ(HeΛ4)-BΛ(HΛ4)=0.35±0.06MeV of the A=4 mirror hypernuclei ground states, determined from emulsion studies, has defied theoretical attempts to reproduce it in terms of CSB in hyperon masses and in hyperon-nucleon interactions, including one pion exchange arising from Λ-σ0 mixing. Using a schematic strong-interaction ΛN↔σN coupling model developed by Akaishi and collaborators for s-shell Λ hypernuclei, we revisit the evaluation of CSB in the A=4 Λ hypernuclei and extend it to p-shell mirror Λ hypernuclei. The model yields values of δBΛ4(0g.s.+)~0.25MeV. Smaller size and mostly negative p-shell binding energy differences are calculated for the A=7-10 mirror hypernuclei, in rough agreement with the few available data. CSB is found to reduce by almost 30 keV the 110 keV BΛ10 g.s. doublet splitting anticipated from the hyperon-nucleon strong-interaction spin dependence, thereby explaining the persistent experimental failure to observe the 2exc-→1g.s.- γ-ray transition. © 2015 The Author.

Gal A.,Hebrew University of Jerusalem | Millener D.J.,Brookhaven National Laboratory
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2013

Recent experimental evidence presented by the FINUDA Collaboration for a particle-stable HΛ6 has stirred renewed interest in charting domains of particle-stable neutron-rich Λ hypernuclei, particularly for unbound nuclear cores. We have studied within a shell-model approach several neutron-rich Λ hypernuclei in the nuclear p shell that could be formed in (π-, K+) or in (K-, π+) reactions on stable nuclear targets. Hypernuclear shell-model input is taken from a theoretically inspired successful fit of γ-ray transitions in p-shell Λ hypernuclei which includes also ΛN↔σN coupling (Λσ coupling). The particle stability of HΛ6 is discussed and predictions are made for binding energies of HeΛ9, LiΛ10, BeΛ12, BΛ14. None of the large effects conjectured by some authors to arise from Λσ coupling is borne out, neither by these realistic p-shell calculations, nor by quantitative estimates outlined for heavier hypernuclei with substantial neutron excess. © 2013 Elsevier B.V.

Itin Y.,Hebrew University of Jerusalem
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

Electromagnetic media with generic linear response provide a rich class of Lorentz violation models. In the framework of a general covariant metric-free approach, we study electromagnetic wave propagation in these media. We define the notion of an optic tensor and present its unique canonical irreducible decomposition into the principle and skewon parts. The skewon contribution to the Minkowski vacuum is a subject that does not arise in the ordinary models of Lorentz violation based on a modified Lagrangian. We derive the covector parametrization of the skewon optic tensor and discuss its U(1)-gauge symmetry. We obtain several compact expressions for the contribution of the principle and skewon optic tensor to the dispersion relation. As an application of the technique proposed here, we consider the case of a generic skewon tensor contributed to a simple metric-type principle part. Our main result: Every solution of the skewon-modified Minkowski dispersion relation is necessarily spacelike or null. It provides an extreme violation of the Lorentz symmetry. The case of the antisymmetric skewon is studied in detail, and some new special cases (electric, magnetic, and degenerate) are discovered. In the case of a skewon represented by a symmetric matrix, we observe a parametric gap that has some similarity to the Higgs model. We worked out a set of specific examples that justify the generic properties of the skewon models and demonstrate the different types of Lorentz violation phenomena. © 2015 American Physical Society.

Bekenstein J.D.,Hebrew University of Jerusalem
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

The statistical response of a Kerr black hole to incoming quantum radiation has heretofore been studied by the methods of maximum entropy or quantum field theory in curved spacetime. Neither approach pretends to take into account the quantum structure of the black hole itself. To address this last issue we calculate here the conditional probability distribution associated with the hole's response by assuming that the horizon area has a discrete quantum spectrum, and that its quantum evolution corresponds to jumps between adjacent area eigenvalues, possibly occurring in series, with consequent emission or absorption of quanta, possibly in the same mode. This "atomic model" of the black hole is implemented in two different ways and recovers the previously calculated radiation statistics in both cases. The corresponding conditional probability distribution is here expressed in closed form in terms of a hypergeometric function. © 2015 American Physical Society.

Human neurodegenerative maladies share two common key features: a mechanistic link to the accumulation and deposition of aberrantly aggregated proteins and late onset. These similarities among otherwise unrelated disorders suggest that the aging process plays an active role in enabling the emergence of these diseases late in life. Invertebrate-based studies have shown that the manipulation of aging by the reduction of the Insulin/IGF signaling (IIS), a prominent aging regulatory pathway, protects model organisms from neurodegeneration-linked toxic protein aggregation. Recent studies have also indicated that the counter proteotoxic effect of IIS reduction is conserved from worms to mice as reduced IGF-1 signaling protected Alzheimer's-model mice from the disease-like behavioral impairments, pathological phenotypes and premature death typical to these model animals. In this article I review the current knowledge on the protective mechanisms that are suppressed by the IIS and discuss the future therapeutic potential of IIS reduction as a treatment for neurodegenerative disorders. © 2010 Elsevier Inc.

Turley E.A.,University of Western Ontario | Naor D.,Hebrew University of Jerusalem
Frontiers in Bioscience | Year: 2012

CD44 and RHAMM are two extracellar matrix receptors whose principle ligand is the polysaccharide hyaluronan (HA). Both proteins are involved in wound repair and their aberrant regulation contributes to a variety of diseases including arthritis and cancer. Over the past decade, a number of peptide-based therapeutics that block the binding of CD44 or RHAMM-specific ligands have been developed and tested in experimental models of disease. Here, we review the structure of each of these proteins, the functions they control and the mechanisms, including their interactions with each other, responsible for these functions. We also review the development of peptide mimics that block the key functions of CD44 and RHAMM and their use in experimental models of disease.

Ben Ishai P.,Hebrew University of Jerusalem
The Review of scientific instruments | Year: 2012

We examine the validity of three common methods for analysis and correction of the electrode polarization (EP) effect in dielectric spectroscopy measurements of conductive liquid samples. The methods considered are (i) algorithmic treatment by modeling the EP behavior at constant phase angle, (ii) varying the size of the electrode gap, and (iii) polypyrrole (PPyPss) layered electrodes. The latter is a relatively recent innovation suggested to be an efficient solution. We demonstrate that PPyPss coated electrodes do not diminish the effect of EP, and even add relaxation processes of its own. Our conclusion is that these polymer coated electrodes are not suitable for the correction of electrode polarization.

Solomon A.,Hebrew University of Jerusalem
Current Opinion in Allergy and Clinical Immunology | Year: 2015

Purpose of review Vernal keratoconjunctivitis (VKC) is a severe bilateral chronic allergic inflammatory disease of the ocular surface. In most of the cases, the disease is limited to the tarsal conjunctiva and to the limbus. However, in the more severe cases, the cornea may be involved, leading to potentially sight threatening complications. Prompt recognition of these complications is crucial in the management of VKC, which is one of the most severe ocular allergic diseases. Recent findings A vicious cycle of inflammation occurs as a result of a set of reciprocal interactions between the conjunctiva and the cornea, which results in damage to the corneal epithelium and corneal stoma, and to the formation of shield ulcers and plaques, infectious keratitis, keratoconus, scarring, and limbal stem cell deficiency. These corneal complications can cause permanent decrease or loss of vision in children suffering from VKC. Summary Corneal complications in VKC are the result of an on-going process of uncontrolled inflammation. Proper recognition of the corneal complications in VKC is crucial, as most of these can be managed or prevented by a combination of medical and surgical measures. © 2015 Wolters Kluwer Health, Inc.

Hagan N.,Harvard University | Ben-Zvi A.,Harvard University | Ben-Zvi A.,Hebrew University of Jerusalem
Seminars in Cell and Developmental Biology | Year: 2015

The blood brain barrier (BBB) is a hallmark of blood vessels in the brain and functions to protect the brain from unwanted blood born materials, support the unique metabolic needs of the brain, and define a stable environment crucial for brain homeostasis. The temporal profile of BBB development was long debated until recent studies produced convincing evidence demonstrating that the BBB is established and functional during embryogenesis. Here we review research focused on the molecular, cellular and morphological characteristics of BBB development. Our review discusses the precise temporal profile of BBB formation, the development of endothelial cell ultrastructure and the molecular components that provide sealing and transporting properties, the molecular pathways involved in the induction of BBB specific endothelial cell differentiation, the signaling pathways driving developmental angiogenesis versus barrier-genesis, and finally the contribution of other cell types to BBB formation. We examine aspects of BBB development that are still unresolved while highlighting research tools that could provide new insight to answer these open questions. © 2014 Elsevier Ltd.

Sompolinsky H.,Hebrew University of Jerusalem | Sompolinsky H.,Harvard University
Current Opinion in Neurobiology | Year: 2014

Computational neuroscience has focused largely on the dynamics and function of local circuits of neuronal populations dedicated to a common task, such as processing a common sensory input, storing its features in working memory, choosing between a set of options dictated by controlled experimental settings or generating the appropriate actions. Most of current circuit models suggest mechanisms for computations that can be captured by networks of simplified neurons connected via simple synaptic weights. In this article I review the progress of this approach and its limitations. It is argued that new experimental techniques will yield data that might challenge the present paradigms in that they will (1) demonstrate the computational importance of microscopic structural and physiological complexity and specificity; (2) highlight the importance of models of large brain structures engaged in a variety of tasks; and (3) reveal the necessity of coupling the neuronal networks to chemical and environmental variables. © 2014 Elsevier Ltd.

Aumann T.D.,University of Melbourne | Prut Y.,Hebrew University of Jerusalem
Trends in Neurosciences | Year: 2015

Coherent β-oscillations are a dominant feature of the sensorimotor system yet their function remains enigmatic. We propose that, in addition to cell intrinsic and/or local network interactions, they are supported by activity propagating recurrently around closed neural 'loops' between primary motor cortex (M1), muscles, and back to M1 via somatosensory pathways. Individual loops reciprocally connect individual muscle synergies ('motor primitives') with their representations in M1, and the conduction time around each loop resonates with the periodic spiking of its constituent neurons/muscles. During β-oscillations, this resonance strengthens within-loop connectivity (via long-term potentiation, LTP), whereas non-resonance between different loops weakens connectivity (via long-term depression, LTD) between M1 representations of different muscle synergies. In this way, β-oscillations help maintain accurate and discrete representations of muscle synergies in M1. © 2014 Elsevier Ltd.

Zaidner Y.,Haifa University | Zaidner Y.,Hebrew University of Jerusalem
PLoS ONE | Year: 2013

The lithic assemblage of the Early Pleistocene site of Bizat Ruhama, Israel demonstrates the earliest evidence for systematic secondary knapping of flakes. The site, dated to the Matuyama chron, is one of the earliest primary context Oldowan occurrences in Eurasia. According to the experimental replication of the stone-tool production sequence, the secondary knapping of flakes was a part of a multi-stage operational sequence targeted at the production of small (<2 cm) flakes. This sequence included four stages: acquisition of chert pebbles, production of flakes, deliberate selection of flakes of specific morphologies, and their secondary knapping by free-hand or bipolar methods. The results suggest that flakes with retouch-like scars that were produced during this sequence and which commonly are interpreted as shaped tools are unintentional waste products of the small flake production. The intentional manufacture of very small flakes at Bizat Ruhama was probably an economic response to the raw material constrains. Systematic secondary knapping of flakes has not yet been reported from other Early Pleistocene sites. Systematic secondary knapping for small flake production became increasingly important only in the lithic industries of the second half of the Middle Pleistocene, almost a million years later. The results from Bizat Ruhama indicate that Oldowan stone-tool production sequence was conceptually more complex than previously suggested and offer a new perspective on the capabilities for invention and the adaptive flexibility of the Oldowan hominins. © 2013 Yossi Zaidner.

Piccinini G.,University of Missouri-St. Louis | Shagrir O.,Hebrew University of Jerusalem
Current Opinion in Neurobiology | Year: 2014

Most computational neuroscientists assume that nervous systems compute and process information. We discuss foundational issues such as what we mean by 'computation' and 'information processing' in nervous systems; whether computation and information processing are matters of objective fact or of conventional, observer-dependent description; and how computational descriptions and explanations are related to other levels of analysis and organization. © 2013.

Gal A.,Hebrew University of Jerusalem
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

A recent lattice QCD (LQCD) calculation of Σ-Λ mixing by the QCDSF-UKQCD Collaboration [Phys. Rev. D 91, 074512 (2015)] finds a mixing angle about half of that found from the Dalitz-Von Hippel (DvH) flavor SU(3) mass formula which relates the Σ-Λ mixing matrix element to known octet baryon mass differences and which has been used widely to evaluate charge symmetry breaking effects in Λ hypernuclei. We show that the LQCD-calculated Σ-Λ mixing matrix element and octet baryon masses satisfy the DvH mass formula, concluding thereby that a good LQCD evaluation of Σ-Λ mixing requires an equally good reproduction of octet baryon mass differences which is yet to be demonstrated. © 2015 American Physical Society.

Kolikant Y.B.-D.,Hebrew University of Jerusalem
Computers in Human Behavior | Year: 2010

In the literature students are sometimes assumed to feel empowered with respect to learning because of their familiarity with and access to ICT. However, after interviewing 25 students from post-elementary schools, it was found that the majority of the students, although they use the Internet and other ICT for school purposes, believed that their generation is not as good at learning as the pre-ICT generation. Several students explained the situation in terms of the school's failure to build on their abilities. Nonetheless, the majority believed that the Internet over-simplifies schoolwork (perceived primarily as the traditional processing of textual sources), which in turn diminishes learning abilities. These results carry important implications regarding school, given that low self-efficacy might make students less likely to apply themselves to learning. © 2010 Elsevier Ltd. All rights reserved.

Hovav A.-H.,Hebrew University of Jerusalem
Mucosal Immunology | Year: 2014

The oral cavity contains distinct mucosal surfaces, each with its own unique distribution of dendritic cell (DC) subsets. In addition to tissue-specific properties, such organization might confer differential immune outcomes guided by tissue-resident DCs, which translate in the lymph node into an overall immune response. This process is further complicated by continual exposure and colonization of the oral cavity with enormous numbers of diverse microbes, some of which might induce destructive immunity. As a central cell type constantly monitoring changes in oral microbiota and orchestrating T-cell function, oral DCs are of major importance in deciding whether to induce immunity or tolerance. In this review, an overview of the phenotype and distribution of DCs in the oral mucosa is provided. In addition, the role of the various oral DC subsets in inducing immunity vs. tolerance, as well as their involvement in several oral pathologies is discussed. © 2014 Society for Mucosal Immunology.

Shouval D.,Hebrew University of Jerusalem | Roggendorf H.,TU Munich | Roggendorf M.,TU Munich
Medical Microbiology and Immunology | Year: 2015

Efficacy and safety of recombinant yeast-derived hepatitis B vaccines for prevention of hepatitis B have been demonstrated unequivocally worldwide as reflected in reduction in HBsAg carrier rates and hepatocellular carcinoma. A new generation of recombinant HBV vaccines expressed in mammalian cells containing Pre-S/S epitopes has been developed in several countries. Such vaccines are useful in special risk groups, i.e., in non-responders to conventional HBV vaccines including older adults, obese people, health care workers, patients with renal failure and on dialysis, transplant patients, patients with HIV as well as travelers on short notice to HBV endemic regions. The future of such vaccines depends on their enhanced immunogenicity and cost profile. Sci-B-Vac™ is a mammalian cell-derived recombinant Pre-S1/Pre-S2/S hepatitis B vaccine which has been shown to be highly immunogenic, inducing faster and higher seroprotection rates against HBV with higher anti-HBs levels at lower HBsAg doses as compared to conventional yeast-derived vaccines. Recently, it has been suggested that such Pre-S/S vaccines against HBV might be efficacious not only for prevention but also for intervention in persistent HBV infection. Data obtained in a recent clinical trial conducted in Vietnam in patients with chronic hepatitis B suggest that repeated monthly i.m. injections of the Sci-B-Vac™ co-administered with daily oral lamivudine treatment can suppress HBV replication and lead to anti-HBs seroconversion in ~50 % of treated patients. Optimization of protocols and efficacy of such an intervention, intended to bypass T cell exhaustion and immune tolerance to HBV remains to be explored. © 2014, The Author(s).

Sonin E.B.,Hebrew University of Jerusalem
Physical Review B - Condensed Matter and Materials Physics | Year: 2013

The paper reassesses the old but still controversial problem of the transverse force on a vortex and the vortex mass. The transverse force from free bulk quasiparticles on the vortex, both in the Bose and the Fermi liquids, originates from the Aharonov-Bohm effect. However, in the Fermi liquid, one should take into account peculiarities of the Aharonov-Bohm effect for BCS quasiparticles described by two-component spinor wave functions. There is no connection between the transverse force (either from free bulk quasiparticles or from vortex-core bound quasiparticles) and the spectral flow in the vortex core in superfluid Fermi liquid, in contrast to widely known claims. In fact, there is no steady spectral flow in the core of the moving vortex, and the analogy with the Andreev bound states in the superconductor-normal-metal-superconductor junction, where the spectral flow is really possible, is not valid in this respect. The role of the backflow on the vortex mass is clarified. The backflow is an inevitable consequence of a mismatch between the currents inside and outside the vortex core and restores the conservation of the particle number (charge) violated by this mismatch. In the Fermi liquid, the backflow compensates the current through the core bound states, which is a source of the vortex mass (the Kopnin mass). This results in renormalization of the Kopnin vortex mass by a numerical factor. © 2013 American Physical Society.

Siegal T.,Hebrew University of Jerusalem
Neuro-Oncology | Year: 2013

The prognosis and treatment outcome for primary brain tumors have remained unchanged despite advances in anticancer drug discovery and development. In clinical trials, the majority of promising experimental agents for brain tumors have had limited impact on survival or time to recurrence. These disappointing results are partially explained by the inadequacy of effective drug delivery to the CNS. The impediments posed by the various specialized physiological barriers and active efflux mechanisms lead to drug failure because of inability to reach the desired target at a sufficient concentration. This perspective reviews the leading strategies that aim to improve drug delivery to brain tumors and their likelihood to change clinical practice.The English literature was searched for defined search items.Strategies that use systemic delivery and those that use local delivery are critically reviewed. In addition, challenges posed for drug delivery by combined treatment with anti-angiogenic therapy are outlined.To impact clinical practice and to achieve more than just a limited local control, new drugs and delivery systems must adhere to basic clinical expectations. These include, in addition to an antitumor effect, a verified favorable adverse effects profile, easy introduction into clinical practice, feasibility of repeated or continuous administration, and compatibility of the drug or delivery system with any tumor size and brain location. © 2013 The Author(s).

Marcus Y.,Hebrew University of Jerusalem
Journal of Supercritical Fluids | Year: 2012

Expressions are derived for the separate solubility parameters of supercritical water (SCW) due to dispersion, polarity, and hydrogen bonding interactions, in terms of the molar volume of SCW. The molar volumes were calculated from established densities, in turn, and the calculated data are presented as a function of the temperature and the pressure in the ranges relevant to applications of SCW: 400-700 °C and 25-100 MPa. © 2011 Elsevier B.V. All rights reserved.

Bloch G.,Hebrew University of Jerusalem
Proceedings. Biological sciences / The Royal Society | Year: 2013

Daily rhythms of physiology and behaviour are governed by an endogenous timekeeping mechanism (a circadian 'clock'). The alternation of environmental light and darkness synchronizes (entrains) these rhythms to the natural day-night cycle, and underlying mechanisms have been investigated using singly housed animals in the laboratory. But, most species ordinarily would not live out their lives in such seclusion; in their natural habitats, they interact with other individuals, and some live in colonies with highly developed social structures requiring temporal synchronization. Social cues may thus be critical to the adaptive function of the circadian system, but elucidating their role and the responsible mechanisms has proven elusive. Here, we highlight three model systems that are now being applied to understanding the biology of socially synchronized circadian oscillators: the fruitfly, with its powerful array of molecular genetic tools; the honeybee, with its complex natural society and clear division of labour; and, at a different level of biological organization, the rodent suprachiasmatic nucleus, site of the brain's circadian clock, with its network of mutually coupled single-cell oscillators. Analyses at the 'group' level of circadian organization will likely generate a more complex, but ultimately more comprehensive, view of clocks and rhythms and their contribution to fitness in nature.

Cohen S.,Hebrew University of Jerusalem
Proceedings of the ACM SIGMOD International Conference on Management of Data | Year: 2013

Given a tree Q and a large set of trees T = {T1,⋯, T n}, the subtree similarity-search problem is that of finding the subtrees of trees among T that are most similar to Q, using the tree edit distance metric. Determining similarity using tree edit distance has been proven useful in a variety of application areas. While subtree similarity-search has been studied in the past, solutions required traversal of all of T, which poses a severe bottleneck in processing time, as T grows larger. This paper proposes the first index structure for subtree similarity-search, provided that the unit cost function is used. Extensive experimentation and comparison to previous work shows the huge improvement gained when using the proposed index structure and processing algorithm. Copyright © 2013 ACM.

Ziv O.,TheHebrew University Hadassah Medical School | Glaser B.,Hebrew University of Jerusalem | Dor Y.,TheHebrew University Hadassah Medical School
Developmental Cell | Year: 2013

Pancreas homeostasis is based on replication of differentiated cells in order to maintain proper organ size and function under changing physiological demand. Recent studies suggest that acinar cells, the most abundant cell type in the pancreas, are facultative progenitors capable of reverting to embryonic-like multipotent progenitor cells under injury conditions associated with inflammation. In parallel, it is becoming apparent that within the endocrine pancreas, hormone-producing cells can lose or switch their identity under metabolic stress or in response to single gene mutations. This new view of pancreas dynamics suggests interesting links between pancreas regeneration and pathologies including diabetes and pancreatic cancer. © 2013 Elsevier Inc.

Jarrous N.,Hebrew University of Jerusalem | Gopalan V.,Ohio State University
Nucleic Acids Research | Year: 2010

RNase P, a catalytic ribonucleoprotein (RNP), is best known for its role in precursor tRNA processing. Recent discoveries have revealed that eukaryal RNase P is also required for transcription and processing of select non-coding RNAs, thus enmeshing RNase P in an intricate network of machineries required for gene expression. Moreover, the RNase P RNA seems to have been subject to gene duplication, selection and divergence to generate two new catalytic RNPs, RNase MRP and MRP-TERT, which perform novel functions encompassing cell cycle control and stem cell biology. We present new evidence and perspectives on the functional diversification of the RNase P RNA to highlight it as a paradigm for the evolutionary plasticity that underlies the extant broad repertoire of catalytic and unexpected regulatory roles played by RNA-driven RNPs. © 2010 The Author(s).

Goldstick O.,Pediatric and Adolescent Gynecology Clinic | Constantini N.,Hebrew University of Jerusalem
British Journal of Sports Medicine | Year: 2014

A literature review was performed on the topic of urinary incontinence during physical activity and sports. This paper reviews the prevalence, risk factors, pathophysiology and treatment modalities of urinary incontinence in physically active women and female athletes. Urinary incontinence affects women of all ages, including top female athletes, but is often underreported. The highest prevalence of urinary incontinence is reported in those participating in high impact sports. Pelvic floor muscle training is considered the first-line treatment, although more research is needed to determine optimal treatment protocols for exercising women and athletes. Trainers, coaches and other athletes' caregivers should be educated and made aware of the need for proper urogynaecological assessment.

Kidron G.J.,Hebrew University of Jerusalem
Journal of Hydrology | Year: 2014

Following recent findings that biocrusts (known also as biological soil crusts) enhance the evaporation of the underlying soil in the dune field in the Negev Desert (P= 95. mm), an attempt is made to evaluate the effect of biocrust on plant germination and growth during drought years. Periodical (mainly weekly) moisture measurements of the upper 30. cm layer were conducted at 5 habitats of formerly defined biocrust types and at 4 non-crusted habitats during 2010/11 and 2011/12 (extreme drought years with 30.4 and 35.2. mm, respectively). At the end of each growing season, the species composition, cover and biomass of the annual plants was measured. While only limited germination and annual-plant maturation took place in the crusted habitats during 2011/12, no germination was recorded at the crusted habitats during 2010/11, explained by enhanced evaporation due to lower albedo of the biocrusts. In contrast, annual-plant germination and maturation took place at the non-crusted habitats during both years. Contrary to the common view that regards sand dunes as infertile and hostile for plant growth while highlighting the positive role of biocrusts on plants, the current findings indicate that as far as annual plant productivity is concerned, the non-crusted dune may serve as a fertility belt for annuals during extreme drought years. © 2013 Elsevier B.V.

The regulation of plant hydraulic conductance and gas conductance involves a number of different morphological, physiological and molecular mechanisms working in harmony. At the molecular level, aquaporins play a key role in the transport of water, as well as CO2, through cell membranes. Yet, their tissue-related function, which controls whole-plant gas exchange and water relations, is less understood. In this study, we examined the tissue-specific effects of the stress-induced tobacco Aquaporin1 (NtAQP1), which functions as both a water and CO2 channel, on whole-plant behavior. In tobacco and tomato plants, constitutive overexpression of NtAQP1 increased net photosynthesis (A(N)), mesophyll CO2 conductance (g(m)) and stomatal conductance (g(s)) and, under stress, increased root hydraulic conductivity (L(pr)) as well. Our results revealed that NtAQP1 that is specifically expressed in the mesophyll tissue plays an important role in increasing both A(N) and g(m). Moreover, targeting NtAQP1 expression to the cells of the vascular envelope significantly improved the plants' stress response. Surprisingly, NtAQP1 expression in the guard cells did not have a significant effect under any of the tested conditions. The tissue-specific involvement of NtAQP1 in hydraulic and gas conductance via the interaction between the vasculature and the stomata is discussed.

Levi M.,Hebrew University of Jerusalem
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

We calculate via the effective field theory (EFT) approach the next-to-next-to-leading order (NNLO) spin1-spin2 conservative potential for a binary. Hereby, we first demonstrate the ability of the EFT approach to go at NNLO in post-Newtonian (PN) corrections from spin effects. The NNLO spin1-spin2 interaction is evaluated at fourth PN order for a binary of maximally rotating compact objects. This sector includes contributions from diagrams, which are not pure spin1-spin2 diagrams, as they contribute through the leading-order spin accelerations and precessions, that should be first taken into account here. The fact that the spin is derivative-coupled adds significantly to the complexity of computations. In particular, for the irreducible two-loop diagrams, which are the most complicated to evaluate in this sector, irreducible two-loop tensor integrals up to order 4 are required. The EFT calculation is carried out in terms of the nonrelativistic gravitational (NRG) fields. However, not all of the benefits of the NRG fields apply to spin interactions, as all possible diagram topologies are realized at each order of G included. Still, the NRG fields remain advantageous, and thus there was no use of automated computations in this work. Our final result can be reduced, and a corresponding Hamiltonian may be derived. © 2012 American Physical Society.

Bekenstein J.D.,Hebrew University of Jerusalem
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

Quantum gravity theory is untested experimentally. Could it be tested with tabletop experiments? While the common feeling is pessimistic, a detailed inquiry shows it possible to sidestep the onerous requirement of localization of a probe on the Planck length scale. I suggest a tabletop experiment which, given state-of-the-art ultrahigh vacuum and cryogenic technology, could already be sensitive enough to detect Planck scale signals. The experiment combines a single photon's degree of freedom with that of a macroscopic probe to test Wheeler's conception of "quantum foam," the assertion that on length scales of the Planck order, spacetime is no longer a smooth manifold. The scheme makes few assumptions beyond energy and momentum conservations, and is not based on a specific quantum gravity scheme. © 2012 American Physical Society.

Tulchinsky T.H.,Hebrew University of Jerusalem
Public Health Reviews | Year: 2010

Micronutrient deficiency conditions are widespread among 2 billion people in developing and in developed countries. These are silent epidemics of vitamin and mineral deficiencies affecting people of all genders and ages, as well as certain risk groups. They not only cause specific diseases, but they act as exacerbating factors in infectious and chronic diseases, greatly impacting morbidity, mortality, and quality of life. Deficiencies in some groups of people at special risk require supplementation, but the most effective way to meet community health needs safely is by population based approaches involving food fortification. These complementary methods, along with food security, education, and monitoring, are challenges for public health and for clinical medicine. Micronutrient deficiency conditions relate to many chronic diseases, such as osteoporosis osteomalacia, thyroid deficiency colorectal cancer and cardiovascular diseases. Fortification has a nearly century long record of success and safety, proven effective for prevention of specific diseases, including birth defects. They increase the severity of infectious diseases, such as measles, HIV/AIDS and tuberculosis. Understanding the pathophysiology and epidemiology of micronutrient deficiencies, and implementing successful methods of prevention, both play a key part in the New Public Health as discussed in this section, citing the examples of folic acid, vitamin B12, and vitamin D.

Ben-Naim A.,Hebrew University of Jerusalem
Current Opinion in Colloid and Interface Science | Year: 2013

It is shown that the solvent induced forces on hydrophilic groups are the strongest ones. The relevance of this finding to protein folding is discussed. © 2013 Elsevier Ltd.

Arkadir D.,Columbia University | Bergman H.,Hebrew University of Jerusalem | Fahn S.,Columbia University
Neurology | Year: 2014

Neurodegenerative diseases become clinically apparent only after a substantial population of neurons is lost. This raises the possibility of compensatory mechanisms in the early phase of these diseases. The importance of understanding these mechanisms cannot be underestimated because it may guide future disease-modifying strategies. Because the anatomy and physiology of the nigrostriatal dopaminergic pathways have been well described, the study of Parkinson disease can offer insight into these early compensatory mechanisms. Collateral axonal sprouting of dopaminergic terminals into the denervated striatum is the most studied compensatory mechanism in animal (almost exclusively rodent) models of Parkinson disease and is correlated with behavioral recovery after partial lesions. This sprouting, however, does not respect the normal anatomy of the original nigrostriatal pathways and leads to aberrant neuronal networks. We suggest here that the unique physiologic property of the dopaminergic innervation of the striatum, namely redundancy of information encoding, is crucial to the efficacy of compensatory axonal sprouting in the presence of aberrant anatomical connections. Redundant information encoding results from the similarity of representation of salient and rewarding events by many dopaminergic neurons, from the wide axonal field of a single dopaminergic neuron in the striatum, and from the nonspecific spatial effect of dopamine on striatal neurons (volume conductance). Finally, we discuss the relevance of these findings in animal models to human patients with Parkinson disease. © 2014 American Academy of Neurology.

Davidovich U.,Hebrew University of Jerusalem
Nature Genetics | Year: 2016

The cereal grass barley was domesticated about 10,000 years before the present in the Fertile Crescent and became a founder crop of Neolithic agriculture. Here we report the genome sequences of five 6,000-year-old barley grains excavated at a cave in the Judean Desert close to the Dead Sea. Comparison to whole-exome sequence data from a diversity panel of present-day barley accessions showed the close affinity of ancient samples to extant landraces from the Southern Levant and Egypt, consistent with a proposed origin of domesticated barley in the Upper Jordan Valley. Our findings suggest that barley landraces grown in present-day Israel have not experienced major lineage turnover over the past six millennia, although there is evidence for gene flow between cultivated and sympatric wild populations. We demonstrate the usefulness of ancient genomes from desiccated archaeobotanical remains in informing research into the origin, early domestication and subsequent migration of crop species. © 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.

Kannai R.,Hebrew University of Jerusalem
Annals of family medicine | Year: 2014

It finally happened to me: I was sued for malpractice by the family of a patient who had died suddenly. My inner turmoil in the aftermath of this traumatic event affected me deeply. While I was an experienced family doctor dedicated to patient-centered medicine, the event challenged my customary approach to my patients. I share three vignettes from my practice that describe my inner dialogue both "preprosecution" and "postprosecution" and explain how I acted in each case. © 2014 Annals of Family Medicine, Inc.

Agmon N.,Hebrew University of Jerusalem
Chemical Physics Letters | Year: 2014

Slater's covalent radii agree nicely with experiment when the effective principal quantum number and the screening constant for the outermost electron are taken from fits of the hydrogen-like energy level expression to ionization energies in isoelectronic series. This establishes a simple connection between the two prominent periodic properties of atoms, namely, their radius and (effective) ionization energy. © 2014 Elsevier B.V. All rights reserved.

Agmon N.,Hebrew University of Jerusalem
Accounts of Chemical Research | Year: 2012

Water deviates from tetrahedral symmetry on different scales, creating "defects" that are important for its dynamics. In this Account, I trace the manifestations of these distortions from the isolated molecule through gas-phase clusters to the liquid phase.Unlike the common depiction, an isolated water molecule has a nonsym-metric charge distribution: although its positive charge is localized at the hydrogens, the negative charge is smeared between the lone-pair sites. This creates a "negativity track" along which a positive charge may slide. Consequently, the most facile motion within the water dimer is a reorientation of the hydrogen-bond (HB) accepting molecule (known as an "acceptor switch"), such that the donor hydrogen switches from one lone pair to the other.Liquid water exhibits asymmetry between donor and acceptor HBs. Molecular dynamics simulations show that the water oxygens accepting HBs from the central molecule are spatially localized, whereas water hydrogens donating HBs to it are distributed along the negativity track. This asymmetry is manifested in a wider acceptor- versus donor-HB distribution. There is a higher probability for a water molecule to accept one (trigonal symmetry) or three HBs than to donate one or three HBs. A simple model can explain semiquantitatively how these distributions evolve by distorting perfectly tetrahedral water. Just two reactions are required: the dissociation of a HB between a double-donor donating to a double-acceptor, D 2⋯ A 2, followed by a switching reaction in which a HB donor rotates its hydrogen between two double-acceptor molecules.The preponderance of D 2⋯A 2 dissociation events is in line with HB "anticooperativity", whereas positive cooperativity is exhibited by conditional HB distributions: a molecule with more acceptor bonds tends to have more donor bonds and vice versa. Quantum mechanically, such an effect arises from intermolecular charge transfer, but it is observed even for fixed-charge water models. Possibly, in the liquid state this is partly a collective effect, for example, a more ordered hydration shell that enhances the probability for both acceptor and donor HBs.The activation energy for liquid water self-diffusion is considerably larger than its HB strength, pointing to the involvement of collective dynamics. The remarkable agreement between the temperature dependence of the water self-diffusion coefficient and its Debye relaxation time suggests that both share the same mechanism, likely consisting of coupled rotation and translation with collective rearrangement of the environment.The auto-correlation function of a hydrogen-bonded water molecule pair is depicted quantitatively by the solution of the diffusion equation for reversible geminate recombination, up to long times where the ubiquitous t -3/2 power law prevails. From the model, one obtains the HB dissociation and formation rate coefficients and their temperature dependence. Both have a similar activation enthalpy, suggesting rapid formation of HBs with alternate partners, perhaps by the HB switching reaction involving the trigonal site.A detailed picture of how small fluctuations evolve into large-scale molecular motions in water remains elusive. Nonetheless, our results demonstrate how the plasticity of water can be traced to its asymmetric charge distribution, with duality between tetrahedral and trigonal ligation states. © 2011 American Chemical Society.

Emmanouil T.A.,City University of New York | Magen H.,Hebrew University of Jerusalem
Trends in Cognitive Sciences | Year: 2014

Behavioral and neural evidence suggests that attention selects entire objects, amplifying all of their features regardless of task relevance. A new magnetoencephalography (MEG) study by Schoenfeld et al. elucidates the time course of this selection, showing that object features are activated sequentially, with attention spreading from task-relevant to task-irrelevant modules. © 2014 Elsevier Ltd.

Dengjel J.,Albert Ludwigs University of Freiburg | Abeliovich H.,Hebrew University of Jerusalem
Autophagy | Year: 2014

Mitophagy, or the autophagic degradation of mitochondria, is thought to be important in mitochondrial quality control, and hence in cellular physiology. Defects in mitophagy correlate with late onset pathologies and aging. Here, we discuss recent results that shed light on the interrelationship between mitophagy and mitochondrial dynamics, based on proteomic analyses of protein dynamics in wild-type and mutant cells. These studies show that different mitochondrial matrix proteins undergo mitophagy at different rates, and that the rate differences are affected by mitochondrial dynamics. These results are consistent with models in which phase separation within the mitochondrial matrix leads to unequal segregation of proteins during mitochondrial fission. Repeated fusion and fission cycles may thus lead to "distillation" of components that are destined for degradation. © 2014 Landes Bioscience.

Mosheiov G.,Hebrew University of Jerusalem
Information Processing Letters | Year: 2011

Most scheduling studies assume constant (position-independent) job processing times. Most of the papers allowing position-dependent processing times consider only special cases, where the job processing times follow a specific function of the job-position. Polynomial time solutions have hardly been found for general position-dependent processing times in scheduling literature. In this note we provide one of these cases: we introduce a polynomial time solution for minimum makespan on an m-machine proportionate flowshop. © 2010 Elsevier B.V. All rights reserved.

Keller N.,Hebrew University of Jerusalem
Combinatorics Probability and Computing | Year: 2011

In this paper we consider the influences of variables on Boolean functions in general product spaces. Unlike the case of functions on the discrete cube, where there is a clear definition of influence, in the general case several definitions have been presented in different papers. We propose a family of definitions for the influence that contains all the known definitions, as well as other natural definitions, as special cases. We show that the proofs of the BKKKL theorem and of other results can be adapted to our new definition. The adaptation leads to generalizations of these theorems, which are tight in terms of the definition of influence used in the assertion. Copyright © Cambridge University Press 2010.

Adam Z.,Hebrew University of Jerusalem
Biochimica et Biophysica Acta - Biomembranes | Year: 2013

Progress in the field of regulated intramembrane proteolysis (RIP) in recent years has made its impact on plant biology as well. Although this field within plant research is still in its infancy, some interesting observations have started to emerge. Gene encoding orthologs of rhomboid proteases, site-2 proteases (S2P), presenilin/γ-secretases, and signal peptide peptidases are found in plant genomes and some of these gene products were identified in different plant cell membranes. The lack of chloroplast-located rhomboid proteases was associated with reduced fertility and aberrations in flower morphology. Mutations in homologues of S2P resulted in chlorophyll deficiency and impaired chloroplast development. An S2P was also implicated in the response to ER stress through cleavage of ER-membrane bZIP transcription factors, allowing their migration to the nucleus and activation of the transcription of BiP chaperones. Other membrane-bound transcription factors of the NAC and PHD families were also demonstrated to undergo RIP and relocalization to the nucleus. These and other new data are expected to shed more light on the roles of intramembrane proteases in plant biology in the future. This article is part of a Special Issue entitled: Intramembrane Proteases. © 2013 Elsevier B.V. All rights reserved.

When do regulatory agencies expand, following the emergence of novel technologies? This article presents a verbal model that suggests that a regulator is most likely to announce that it has statutory authority to regulate a novel technology when its reputation is at stake. This is most likely to occur when (1) new information becomes available to the regulator regarding the seriousness of the anticipated harm of a novel technology, or (2) a rival regulator attempts to formalize its regulatory authority or fails to do so although officially required to. A historical-institutional analysis of the temporal process leading to jurisdictional claims by the U.S. Food and Drug Administration over gene therapy, laboratory-developed complex diagnostic tests, human tissue transplants, and human cloning supports the model's prediction. © 2010 Wiley Periodicals, Inc.

Litwin H.,Hebrew University of Jerusalem
Journals of Gerontology - Series B Psychological Sciences and Social Sciences | Year: 2010

Objectives. This study examined whether the social networks of older persons in Mediterranean and non-Mediterranean countries were appreciably different and whether they functioned in similar ways in relation to well-being outcomes. Methods.The sample included family household respondents aged 60 years and older from the first wave of the Survey of Health, Ageing and Retirement in Europe in 5 Mediterranean (n = 3,583) and 7 non-Mediterranean (n = 5,471) countries. Region was regressed separately by gender on variables from 4 network domains: structure and interaction, exchange, engagement and relationship quality, and controlling for background and health characteristics. In addition, 2 well-being outcomes - depressive symptoms and perceived income inadequacy - were regressed on the study variables, including regional social network interaction terms. Results.The results revealed differences across the 2 regional settings in each of the realms of social network, above and beyond the differences that exist in background characteristics and health status. The findings also showed that the social network variables had different effects on the well-being outcomes in the respective settings. Discussion.The findings underscore that the social network phenomenon is contextually bound. The social networks of older people should be seen within their unique regional milieu and in relation to the values and social norms that prevail in different sets of societies. © The Author 2009. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved.

Marcus Y.,Hebrew University of Jerusalem
Pure and Applied Chemistry | Year: 2010

Water is a highly structured liquid, as indicated by its stiffness (cohesive energy density) and being ordered (large entropy of vaporization), its three-dimensional hydrogenbonded network being its most outstanding feature. The extent of this network depends on the definition of the hydrogen bond, and both computer simulation and thermodynamic data yield a consistent picture. The effects of ions on this network in dilute aqueous solutions have been studied from dynamic, thermodynamic, spectroscopic, and computer simulation aspects. A classification of ions from those that are highly water-structure-breaking ions through borderline cases to those that are highly water-structure-making ions results from such studies. Copyright © 2010 IUPAC, Publication date (Web): 19 June 2010.

Ornoy A.,Hebrew University of Jerusalem | Koren G.,Israeli Teratology Information Service
Seminars in Fetal and Neonatal Medicine | Year: 2014

There has been an increase in the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy. However, in the last 10 years, in spite of a vast literature regarding use in pregnancy there seems to be some confusion as to the possible risk of these drugs, especially related to cardiovascular anomalies. In addition, there are data on developmental follow-up studies that raise the question of possible slight developmental and neurobehavioral problems. The purpose of the present review is therefore to critically summarize the current evidence for the risk/benefit analysis of SSRI use in human pregnancy. Although most studies have not shown an increase in the overall risk of major malformations, several have suggested that the use of SSRIs may be associated with a small increased risk for cardiovascular malformations. However, new compelling evidence shows that this apparent increased risk occurs also in women with untreated depression, highlighting the probable ascertainment bias involved in many of these studies. Persistent pulmonary hypertension of the newborn (PPHN) has also been described with an absolute risk of <1%; however, here too, higher rates were described among offspring of women with untreated depression. Poor neonatal adaptation has been described in up to 30% of neonates exposed to SSRIs late in pregnancy. Of the few postnatal developmental follow-up studies, there are no significant developmental problems. The literature on SSRIs in pregnancy is somewhat confusing but when analysing all prospective cohort data there seems to be no demonstrable increase in the rate of major anomalies or developmental disorders. When evaluating the risk/benefit ratio of SSRI treatment in pregnancy, the risk associated with treatment discontinuation - e.g. higher frequency of relapse, increased risk of preterm delivery and postpartum depression - appear to outweigh the potential, unproven risks of treatment. Moreover, maternal depression may negatively affect the child's development, emphasizing the importance of prevention by appropriate treatment during pregnancy with the least minimal effective dose. © 2014 Elsevier Ltd.

Marcus Y.,Hebrew University of Jerusalem
Langmuir | Year: 2013

Surface tension increments by aqueous electrolytes, kE = [γ(cE) - γ(W)]/cE, can be split into the ionic values, ki (kE = Σνiki), on an arbitrary but plausible manner, notwithstanding the effects of counterions on the behavior of specific ions. Values for 41 ions, mono- and polyatomic and uni- and multivalent, are presented in conjunction with some other ionic properties. The surface potential increments of electrolytes, ΔΔχ = ΔχE (at cE = 1 M) - ΔχW, depend linearly on the kE values for four anion series with common cations and on the differences between cation and anion ki values. The ki (normalized to unit charge number) are correlated linearly with the ionic radii ri, the excess ionic molar refractivity over that of water, RDi - RDW, the ionic softness parameters (modified by adding +0.5 to anion and -0.5 to cation values), σ±0.5, and to the geometrical factor of water structure making/breaking, ΔHBG. No correlation takes place with the ionic polarization corrected for that of water, α i* = αi - αW(r i/rW)3, nor with the molar Gibbs energy or enthalpy of hydration. The latter fact implies that ion dehydration does not play a major role in the sorption/desorption of ions at the surface. The correlations that were found are discussed in a qualitative manner and compared with theoretical arguments in the literature. © 2013 American Chemical Society.

Portman M.E.,Hebrew University of Jerusalem
ICES Journal of Marine Science | Year: 2011

Coastal states and nations are conducting marine spatial planning (MSP) at an ever-increasing pace. Some MSP efforts are aimed at planning areas at a subnational level, whereas others extend as far as 200 nautical miles from shore, within national exclusive economic zones. For planning of all types, but especially for planning in the marine realm, integration has become a sought-after norm now that traditional sectoral, single-issue management has not succeeded. Fisheries collapse, threats to marine biodiversity, and global climate change all support the case for greater integration in marine resource management and policy. The designation of boundaries can be related to the level of cross-sector and cross-jurisdictional integration achieved by MSP. The importance of scale and scope for MSP initiatives is examined, relating these aspects of plans and/or programmes to the levels of integration achieved, and a framework is suggested for evaluation. MSP initiatives in Portugal, the UK, and the USA serve as potential case studies for use of the framework. © 2011 International Council for the Exploration of the Sea.

Gagnon A.C.,California Institute of Technology | Adkins J.F.,California Institute of Technology | Erez J.,Hebrew University of Jerusalem
Earth and Planetary Science Letters | Year: 2012

Cation transport during skeletal growth is a key process controlling metal/calcium (Me/Ca) paleoproxy behavior in coral. To characterize this transport, cultured corals were transferred into seawater enriched in the rare earth element Tb 3+ as well as stable isotopes of calcium, strontium, and barium. Subsequent NanoSIMS ion images of each coral skeleton were used to follow uptake dynamics. These images show a continuous region corresponding to new growth that is homogeneously enriched in each tracer. Isotope ratio profiles across the new growth boundary transition rapidly from natural abundance ratios to a ratio matching the enriched culture solution. The location of this transition is the same for each element, within analytical resolution. The synchronous incorporation of all these cations, including the dissimilar ion terbium, which has no known biological function in coral, suggests that: (1) there is cation exchange between seawater and the calcifying fluid, and (2) these elements are influenced by similar transport mechanisms consistent with direct and rapid seawater transport to the site of calcification. Measured using isotope ratio profiles, seawater transport rates differ from place to place on the growing coral skeleton, with calcifying fluid turnover times from 30min to 5.7h. Despite these differences, all the elements measured in this study show the same transport dynamics at each location. Using an analytical geochemical model of biomineralization that includes direct seawater transport we constrain the role of active calcium pumping during calcification and we show that the balance between seawater transport and precipitation can explain observed Me/Ca variability in deep-sea coral. © 2012 .

Kanarek N.,Hebrew University of Jerusalem
Cold Spring Harbor perspectives in biology | Year: 2010

The key step in NF-kappaB activation is the release of the NF-kappaB dimers from their inhibitory proteins, achieved via proteolysis of the IkappaBs. This irreversible signaling step constitutes a commitment to transcriptional activation. The signal is eventually terminated through nuclear expulsion of NF-kappaB, the outcome of a negative feedback loop based on IkappaBalpha transcription, synthesis, and IkappaBalpha-dependent nuclear export of NF-kappaB (Karin and Ben-Neriah 2000). Here, we review the process of signal-induced IkappaB ubiquitination and degradation by comparing the degradation of several IkappaBs and discussing the characteristics of IkappaBs' ubiquitin machinery.

Horowitz M.,Hebrew University of Jerusalem
Frontiers in bioscience (Scholar edition) | Year: 2010

Plasticity of the thermoregulatory system is a key factor for the induction of heat acclimation. Temperature-adaptive shifts in gene expression play an essential role in the processes involved. This review attempts to bridge the gap between the classical physiological heat acclimation profile and the molecular/cellular mechanisms underlying the evolution of the acclimated phenotype. Essential acclimatory modifications linked with thermal tolerance are (i) neuronal plasticity (ii) cytoprotection. Leftward and rightward threshold shifts in these respective functional categories expand the dynamic thermoregulatory range of the acclimated phenotype. Neural plasticity depends on changes in hypothalamic warm/cold sensitive neuron ratio and excitability. Over the course of acclimation, there is marked upregulation of transcripts encoding voltage dependent K+ and Ca2+ channels, neurotransmitters and/or their receptors. Temperature threshold for thermal injury is associated with progressive enhancement of inducible cytoprotective networks including the essential acclimatory components HSP70, HSF1 and HIF-1. Via cross-tolerance, achieved through shared on-call cytoprotective networks, acclimation also renders protection against novel stressors. Collectively, heat acclimation is a within life evolutionarily beneficial phenomenon with a memory, imprinted via epigenetic mechanisms.

Benoliel R.,Hebrew University of Jerusalem
Journal of orofacial pain | Year: 2012

To field-test carefully designed criteria for pain following trigeminal nerve trauma. In order to characterize the clinical phenotype, posttraumatic pain patients were studied and compared with classical trigeminal neuralgia patients (CTN, defined according to the International Headache Society's criteria). Based on etiology and features, trigeminal pain following trauma was defined as "peripheral painful traumatic trigeminal neuropathy" (PPTTN). Data were analyzed with t tests, ANOVA, chi-square, and regression analyses. A total of 145 patients were included: 91 with PPTTN and 54 with CTN. Findings indicated that PPTTN criteria are clinically applicable in the detection and characterization of relevant cases. In contrast to accepted characteristics for PPTTN, the observed profile included both continuous and paroxysmal pain that was stabbing and/or burning. The quality, duration, and intensity were significantly different from the CTN patients (P < .05). PPTTN was consistently accompanied by trigeminal sensory abnormalities (96%) that were mostly allodynia, hyperor hypoalgesia, and only 1% of the PPTTN cases had anesthesia. Overall, the proposed PPTTN criteria have proven to be clinically useful. In view of these results, modified PPTTN diagnostic criteria are proposed for use in future research.

Kanold P.O.,University of Maryland University College | Nelken I.,Hebrew University of Jerusalem | Polley D.B.,Harvard University | Polley D.B.,Massachusetts Eye and Ear Infirmary
Trends in Neurosciences | Year: 2014

Topographic organization is a hallmark of sensory cortical organization. Topography is robust at spatial scales ranging from hundreds of microns to centimeters, but can dissolve at the level of neighboring neurons or subcellular compartments within a neuron. This dichotomous spatial organization is especially pronounced in the mouse auditory cortex, where an orderly tonotopic map can arise from heterogeneous frequency tuning between local neurons. Here, we address a debate surrounding the robustness of tonotopic organization in the auditory cortex that has persisted in some form for over 40 years. Drawing from various cortical areas, cortical layers, recording methodologies, and species, we describe how auditory cortical circuitry can simultaneously support a globally systematic, yet locally heterogeneous representation of this fundamental sound property. © 2014 Elsevier Ltd.

Oren A.,Hebrew University of Jerusalem | Garrity G.M.,Michigan State University
Antonie van Leeuwenhoek, International Journal of General and Molecular Microbiology | Year: 2014

In the 80 years that have passed since the first issue of Antonie van Leeuwenhoek was published, the field of prokaryote systematics has changed dramatically. The 4th edition of Bergey's Manual of Determinative Bacteriology (1934) described 132 genera and 2,703 species. The numbers of genera and species with names with standing in the nomenclature in August 2013 were 2,390 and 11,482, respectively, including no more than 75 genera and 250 species that were recognized in 1934. In the years 2006-2012, on average 624 new species were added annually, most of which were described by scientists in Asian countries. We review the past and current species concept for the prokaryotes and the current requirements for the description of new species, based on a 'polyphasic' approach. We discuss the impact of genomics and metagenomics and other new trends toward revitalization of prokaryote systematics, and provide some ideas and speculations on possible future developments in the field. © 2014 Springer Science+Business Media.

Feuerstein O.,Hebrew University of Jerusalem
Advances in dental research | Year: 2012

Conventional antibacterial treatment fails to eradicate biofilms associated with common infections of the oral cavity. Unlike chemical agents, which are less effective than anticipated, owing to diffusion limitations in biofilms, light is more effective on bacteria in biofilm than in suspension. Effectiveness depends also on the type and parameters of the light. We tested the phototoxic effects of non-coherent blue light (wavelengths, 400-500 nm) and CO(2) laser (wavelength, 10.6 μm), which have different mechanisms of action on the oral bacterium Streptoccocus mutans, in biofilm and on tooth enamel. Exposure of S. mutans in biofilm to blue light had a delayed effect on bacterial viability throughout the biofilm and a sustained antibacterial effect on biofilm newly formed by previously irradiated bacteria. A synergistic antibacterial effect between blue light and H(2)O(2) may enhance the phototoxic effect, which involves a photochemical mechanism mediated by reactive oxygen species (ROS) formation. The effect of CO(2) laser irradiation on the viability of S. mutans in biofilm on enamel samples appeared to be higher in the deep layers, due to heating of the enamel surface by the absorbed energy. Biofilms do not interfere with the chemical changes resulting from irradiation, which may increase the enamel's resistance to acid attack.

Fineberg J.,Hebrew University of Jerusalem
Nature Materials | Year: 2011

The amorphous layer formed on the contact surface of diamonds results from the protruding crystal atoms that pluck each other off the opposing surfaces during polishing. This process builds up an amorphous carbon layer whose thickness is determined by how difficult it is to pluck an atom off the neighboring diamond surfaces. The amorphous, diamond-like carbon (DLC) material composing the layer is itself quite hard. Using atomic potentials previously derived to describe the fracture of carbon bonds, Pastewka and colleagues demonstrated good quantitative agreement with the dependence of experimental wear rates on crystal orientation and polishing direction. When surfaces are sufficiently rough, however, friction suddenly becomes substantial. Both friction and wear are very sensitive to the conditions at the sliding interface. This sensitivity results from the fact that the load-supporting contacts that compose the interface are both discrete and relatively few in number.

Marcus Y.,Hebrew University of Jerusalem
Journal of Chemical and Engineering Data | Year: 2012

The value of the viscosity B-coefficient of the thiocyanate anion reported in the biophysical literature, B η(SCN -) = -0.103 dm 3·mol -1, is erroneous. It is not derived from direct viscosity measurements. It should be replaced by -0.032 ± 0.006 dm 3·mol -1 at 25 °C, the average from values derived from viscosity measurements. © 2012 American Chemical Society.

Palamara P.F.,Columbia University | Lencz T.,North Shore Long Island Jewish Health System | Darvasi A.,Hebrew University of Jerusalem | Pe'er I.,Columbia University
American Journal of Human Genetics | Year: 2012

Data-driven studies of identity by descent (IBD) were recently enabled by high-resolution genomic data from large cohorts and scalable algorithms for IBD detection. Yet, haplotype sharing currently represents an underutilized source of information for population-genetics research. We present analytical results on the relationship between haplotype sharing across purportedly unrelated individuals and a population's demographic history. We express the distribution of IBD sharing across pairs of individuals for segments of arbitrary length as a function of the population's demography, and we derive an inference procedure to reconstruct such demographic history. The accuracy of the proposed reconstruction methodology was extensively tested on simulated data. We applied this methodology to two densely typed data sets: 500 Ashkenazi Jewish (AJ) individuals and 56 Kenyan Maasai (MKK) individuals (HapMap 3 data set). Reconstructing the demographic history of the AJ cohort, we recovered two subsequent population expansions, separated by a severe founder event, consistent with previous analysis of lower-throughput genetic data and historical accounts of AJ history. In the MKK cohort, high levels of cryptic relatedness were detected. The spectrum of IBD sharing is consistent with a demographic model in which several small-sized demes intermix through high migration rates and result in enrichment of shared long-range haplotypes. This scenario of historically structured demographies might explain the unexpected abundance of runs of homozygosity within several populations. © 2012 The American Society of Human Genetics.

Ilan Y.,Hebrew University of Jerusalem
Hepatology International | Year: 2013

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide. Currently, there are no treatment options available for a large number of these patients. One of the mechanisms that may contribute to tumor growth is the lack of an effective immune response toward viral antigens or other tumor-associated antigens (TAAs). Immunotherapy has been tested as a potential therapeutic option for these patients. Several methods of immune modulation for augmenting antitumor immunity are being explored and have been shown to be effective in suppressing HCC growth in animal models. Activation of HCC-specific response can be accomplished by targeting hepatitis B or C viral antigens, alpha-fetoprotein, or other TAAs. This review summarizes part of the recent data on the use of adoptive transfer of immunity against viral antigens, oral immune modulation against TAAs, and the use of pulsed innate immune cells and gut adjuvants for the suppression of HCC; it reviews some additional new immunotherapeutic approaches. © 2013, Asian Pacific Association for the Study of the Liver.

Reichmann D.,Hebrew University of Jerusalem | Jakob U.,University of Michigan
Current Opinion in Structural Biology | Year: 2013

Cells are constantly exposed to various oxidants, either generated endogenously due to metabolic activity or exogenously. One way that cells respond to oxidants is through the action of redox-regulated proteins. These proteins also play important roles in oxidant signaling and protein biogenesis events. The key sensors built into redox-regulated proteins are cysteines, which undergo reversible thiol oxidation in response to changes in the oxidation status of the cellular environment. In this review, we discuss three examples of redox-regulated proteins found in bacteria, mitochondria, and chloroplasts. These proteins use oxidation of their redox-sensitive cysteines to reversibly convert large structural domains into more disordered regions or vice versa. These massive structural rearrangements are directly implicated in the functions of these proteins. © 2013 Elsevier Ltd.

Atlas D.,Hebrew University of Jerusalem
Annual Review of Biochemistry | Year: 2013

Transmitter release is a fast Ca2+-dependent process triggered in response to membrane depolarization. It involves two major calcium-binding proteins, the voltage-gated calcium channel (VGCC) and the vesicular protein synaptotagmin (syt1). Ca2+ binding triggers transmitter release with a time response of conformational changes that are too fast to be accounted for by Ca2+ binding to syt1. In contrast, conformation-triggered release, which engages Ca2+ binding to VGCC, better accounts for the fast rate of the release process. Here, we summarize findings obtained from heterologous expression systems, neuroendocrine cells, and reconstituted systems, which reveal the molecular mechanism by which Ca2+ binding to VGCC triggers exocytosis prior to Ca2+ entry into the cell. This review highlights the molecular aspects of an intramembrane signaling mechanism in which a signal is propagated from the channel transmembrane (TM) domain to the TM domain of syntaxin 1A to trigger transmitter release. It discusses fundamental problems of triggering transmitter release by syt1 and suggests a classification of docked vesicles that might explain synchronous transmitter release, spontaneous release, and facilitation of transmitter release. © 2013 by Annual Reviews. All rights reserved.

Yagel S.,Hebrew University of Jerusalem
Thrombosis Research | Year: 2011

Vascular endothelial growth factor (VEGF) is a key player in vasculogenesis and angiogenesis in the embryo, and essential in neovascularization in adults. Natural VEGF inhibitors such as soluble VEGF receptors, among them the soluble VEGF-trapping receptor Flt1 (sFlt1), participate in VEGF regulation. Decreased levels of VEGF and increased levels of sFlt1 have been implicated in the pathophysiology of preeclampsia. We discovered a soluble receptor, sFlt1-14, qualitatively different from sFlt1 and a potent VEGF inhibitor. It is generated in a cell type specific fashion, primarily in nonendothelial cells, most notably in vascular smooth muscle cells. We showed that increased production of soluble VEGF receptors in pregnancy is owing to expression of sFlt1-14, from the end of the first trimester to term. This expression is markedly elevated in preeclampsia, and is expressed chiefly by syncitial knots. In subsequent studies we found that sFlt1 is a strong heparin binder: this capability enables it to stay attached to blood vessels and to the placenta. Ex vivo, sFlt1 can be heparin displaced to medium from aortic segments and placental villi. In vivo, pregnant women treated with the low molecular weight heparin (LMWH) have elevated sFlt1 levels in their circulations. Interestingly, LMWH raised VEGF levels over and above the increase in sFlt1 levels in these patients. Heparanaseoverexpressing non-pregnant as well as pregnant transgenic mice present elevated levels of sFlt1 in their circulations. Ex vivo prevention of heparanase maturation through cathepsin L inhibition, or targeting heparanase directly with a neutralizing antibody, both resulted in a marked reduction in sFlt1 secretion to medium of normal and preeclamptic placental expiants. These findings uncover a new level of regulation that controls sFlt1 bio-distribution, and directs it to function in the vicinity of its producing cell. Heparanase or LMWH has the ability to liberate sFlt1 from its retention, so this process may be a potential target for preeclampsia treatment. © 2010 Elsevier B.V. All rights reserved.

Ben-Chetrit E.,Hebrew University of Jerusalem
Clinical and Experimental Rheumatology | Year: 2014

Objective: To review the current available literature on the mutual effect of pregnancy or contraceptives and Behçet's disease (BD) in order to guide our patients more wisely before they take contraceptives or decide to conceive. Methods: We performed a systematic review of the literature regarding the above issues using PubMed, Cochrane and EMBase databases. Results: We have found 21 case reports and 11 series dealing with the mutual effect of pregnancy or contraceptives and Behçet's disease and 5 case reports dealing with BD and contraceptives. In most cases the course of BD was ameliorated or unchanged during pregnancy. The outcome of pregnancy in BD patients was poorer than that in healthy individuals. Contraceptives have various effects on the course of BD. Conclusions: Despite the above impression, it is quite difficult to predict the course of the disease during pregnancy in an individual BD patient. Patients with BD and a history of thrombosis are recommended to avoid contraceptive pills. © Clinical and Experimental Rrheumatology 2014.

Tamir M.,Hebrew University of Jerusalem | Ford B.Q.,University of Denver
Emotion | Year: 2012

According to the instrumental approach to emotion regulation, people may want to experience even unpleasant emotions to attain instrumental benefits. Building on value-expectancy models of self-regulation, we tested whether people want to feel bad in certain contexts specifically because they expect such feelings to be useful to them. In two studies, participants were more likely to try to increase their anger before a negotiation when motivated to confront (vs. collaborate with) a negotiation partner. Participants motivated to confront (vs. collaborate with) their partner expected anger to be more useful to them, and this expectation in turn, led them to try to increase their anger before negotiating. The subsequent experience of anger, following random assignment to emotion inductions (Study 1) or engagement in self-selected emotion regulation activities (Study 2), led participants to be more successful at getting others to concede to their demands, demonstrating that emotional preferences have important pragmatic implications.

Zakay-Rones Z.,Hebrew University of Jerusalem
Expert Review of Vaccines | Year: 2010

Influenza is responsible for the infection of approximately 20% of the population every season and for an annual death toll of approximately half a million people. The most effective means for controlling infection and thereby reducing morbidity and mortality is vaccination by injection with an inactivated vaccine, or by intranasal administration of a live-attenuated vaccine. Protection is not always optimal and there is a need for the development of new vaccines with improved efficacy and for the expansion of enrollment into vaccination programs. An overview of old and new vaccines is presented. Methods of monitoring immune responses such as hemagglutination-inhibition, ELISA and neutralization tests are evaluated for their accuracy in the assessment of current and new-generation vaccines. © 2010 Expert Reviews Ltd.

Protein-DNA interactions play a key role in the regulation of major cellular metabolic pathways, including gene expression, genome replication, and genomic stability. They are mediated through the interactions of regulatory proteins with their specific DNA-binding sites at promoters, enhancers, and replication origins in the genome. Redox signaling regulates these protein-DNA interactions using reactive oxygen species and reactive nitrogen species that interact with cysteine residues at target proteins and their regulators. This review describes the redox-mediated regulation of several master regulators of gene expression that control the induction and suppression of hundreds of genes in the genome, regulating multiple metabolic pathways, which are involved in cell growth, development, differentiation, and survival, as well as in the function of the immune system and cellular response to intracellular and extracellular stimuli. It also discusses the role of redox signaling in protein-DNA interactions that regulate DNA replication. Specificity of redox regulation is discussed, as well as the mechanisms providing several levels of redox-mediated regulation, from direct control of DNA-binding domains through the indirect control, mediated by release of negative regulators, regulation of redox-sensitive protein kinases, intracellular trafficking, and chromatin remodeling. © 2010, Mary Ann Liebert, Inc.

Atlas D.,Hebrew University of Jerusalem
Cellular Signalling | Year: 2010

Voltage-gated calcium channels (VGCC) are involved in a large variety of cellular Ca2+ signaling processes, including exocytosis, a Ca2+ dependent release of neurotransmitters and hormones.Great progress has been made in understanding the mode of action of VGCC in exocytosis, a process distinguished by two sequential yet independent Ca2+ binding reactions. First, Ca2+ binds at the selectivity filter, the EEEE motif of the VGCC, and second, subsequent to a brief and intense Ca2+ inflow to synaptotagmin, a vesicular protein. Inquiry into the functional and physical interactions of the channels with synaptic proteins has demonstrated that exocytosis is triggered during the initial Ca2+ binding at the channel pore, prior to Ca2+ entry. Accordingly, a cycle of secretion begins by an incoming stimulus that releases vesicles from a releasable pool upon Ca2+ binding at the pore, and at the same time, the transient increase in [Ca2+]i primes a fresh set of non-releasable vesicles, to be fused by the next incoming stimulus.We propose a model, in which the Ca2+ binding at the EEEE motif and the consequent conformational changes in the channel are the primary event in triggering secretion, while synaptotagmin acts as a vesicle docking protein. Thus, the channel serves as the molecular On/Off signaling switch, where the predominance of a conformational change in Ca2+-bound channel provides for the fast secretory process. © 2010 Elsevier Inc.

Minke B.,Hebrew University of Jerusalem
Journal of Neurogenetics | Year: 2010

Transient receptor potential (TRP) channels are polymodal cellular sensors involved in a wide variety of cellular processes, mainly by changing membrane voltage and increasing cellular Ca2. This review outlines in detail the history of the founding member of the TRP family, the Drosophila TRP channel. The field began with a spontaneous mutation in the trp gene that led to a blind mutant during prolonged intense light. It was this mutant that allowed for the discovery of the first TRP channels. A combination of electrophysiological, biochemical, Ca2 measurements, and genetic studies in flies and in other invertebrates pointed to TRP as a novel phosphoinositide-regulated and Ca2-permeable channel. The cloning and sequencing of the trp gene provided its molecular identity. These seminal findings led to the isolation of the first mammalian homologues of the Drosophila TRP channels. We now know that TRP channel proteins are conserved through evolution and are found in most organisms, tissues, and cell-types. The TRP channel superfamily is classified into seven related subfamilies: TRPC, TRPM, TRPV, TRPA, TRPP, TRPML, and TRPN. A great deal is known today about participation of TRP channels in many biological processes, including initiation of pain, thermoregulation, salivary fluid secretion, inflammation, cardiovascular regulation, smooth muscle tone, pressure regulation, Ca 2 and Mg2 homeostasis, and lysosomal function. The native Drosophila photoreceptor cells, where the founding member of the TRP channels superfamily was found, is still a useful preparation to study basic features of this remarkable channel. © 2010 Informa Healthcare USA, Inc.