Showing papers by "Tel Aviv University published in 2002"

Impact of Transformational Leadership on Follower Development and Performance: A Field Experiment

Abstract: In a longitudinal, randomized field experiment, we tested the impact of transformational leadership, enhanced by training, on follower development and performance. Experimental group leaders received transformational leadership training, and control group leaders, eclectic leadership training. The sample included 54 military leaders, their 90 direct followers, and 724 indirect followers. Results indicated the leaders in the experimental group had a more positive impact on direct followers' development and on indirect followers' performance than did the leaders in the control group.

Blobworld: image segmentation using expectation-maximization and its application to image querying

Abstract: Retrieving images from large and varied collections using image content as a key is a challenging and important problem We present a new image representation that provides a transformation from the raw pixel data to a small set of image regions that are coherent in color and texture This "Blobworld" representation is created by clustering pixels in a joint color-texture-position feature space The segmentation algorithm is fully automatic and has been run on a collection of 10,000 natural images We describe a system that uses the Blobworld representation to retrieve images from this collection An important aspect of the system is that the user is allowed to view the internal representation of the submitted image and the query results Similar systems do not offer the user this view into the workings of the system; consequently, query results from these systems can be inexplicable, despite the availability of knobs for adjusting the similarity metrics By finding image regions that roughly correspond to objects, we allow querying at the level of objects rather than global image properties We present results indicating that querying for images using Blobworld produces higher precision than does querying using color and texture histograms of the entire image in cases where the image contains distinctive objects

Support vector clustering

Abstract: We present a novel clustering method using the approach of support vector machines. Data points are mapped by means of a Gaussian kernel to a high dimensional feature space, where we search for the minimal enclosing sphere. This sphere, when mapped back to data space, can separate into several components, each enclosing a separate cluster of points. We present a simple algorithm for identifying these clusters. The width of the Gaussian kernel controls the scale at which the data is probed while the soft margin constant helps coping with outliers and overlapping clusters. The structure of a dataset is explored by varying the two parameters, maintaining a minimal number of support vectors to assure smooth cluster boundaries. We demonstrate the performance of our algorithm on several datasets.

HIV preferentially infects HIV-specific CD4 + T cells

Abstract: HIV infection is associated with the progressive loss of CD4(+) T cells through their destruction or decreased production. A central, yet unresolved issue of HIV disease is the mechanism for this loss, and in particular whether HIV-specific CD4(+) T cells are preferentially affected. Here we show that HIV-specific memory CD4(+) T cells in infected individuals contain more HIV viral DNA than other memory CD4(+) T cells, at all stages of HIV disease. Additionally, following viral rebound during interruption of antiretroviral therapy, the frequency of HIV viral DNA in the HIV-specific pool of memory CD4(+) T cells increases to a greater extent than in memory CD4(+) T cells of other specificities. These findings show that HIV-specific CD4(+) T cells are preferentially infected by HIV in vivo. This provides a potential mechanism to explain the loss of HIV-specific CD4(+) T-cell responses, and consequently the loss of immunological control of HIV replication. Furthermore, the phenomenon of HIV specifically infecting the very cells that respond to it adds a cautionary note to the practice of structured therapy interruption.

Principles of docking: An overview of search algorithms and a guide to scoring functions

Abstract: The docking field has come of age. The time is ripe to present the principles of docking, reviewing the current state of the field. Two reasons are largely responsible for the maturity of the computational docking area. First, the early optimism that the very presence of the "correct" native conformation within the list of predicted docked conformations signals a near solution to the docking problem, has been replaced by the stark realization of the extreme difficulty of the next scoring/ranking step. Second, in the last couple of years more realistic approaches to handling molecular flexibility in docking schemes have emerged. As in folding, these derive from concepts abstracted from statistical mechanics, namely, populations. Docking and folding are interrelated. From the purely physical standpoint, binding and folding are analogous processes, with similar underlying principles. Computationally, the tools developed for docking will be tremendously useful for folding. For large, multidomain proteins, domain docking is probably the only rational way, mimicking the hierarchical nature of protein folding. The complexity of the problem is huge. Here we divide the computational docking problem into its two separate components. As in folding, solving the docking problem involves efficient search (and matching) algorithms, which cover the relevant conformational space, and selective scoring functions, which are both efficient and effectively discriminate between native and non-native solutions. It is universally recognized that docking of drugs is immensely important. However, protein-protein docking is equally so, relating to recognition, cellular pathways, and macromolecular assemblies. Proteins function when they are bound to other molecules. Consequently, we present the review from both the computational and the biological points of view. Although large, it covers only partially the extensive body of literature, relating to small (drug) and to large protein-protein molecule docking, to rigid and to flexible. Unfortunately, when reviewing these, a major difficulty in assessing the results is the non-uniformity in the formats in which they are presented in the literature. Consequently, we further propose a way to rectify it here.

A box-fitting algorithm in the search for periodic transits

Abstract: We study the statistical characteristics of a box-fitting algorithm to analyze stellar photometric time series in the search for periodic transits by extrasolar planets. The algorithm searches for signals characterized by a periodic alternation between two discrete levels, with much less time spent at the lower level. We present numerical as well as analytical results to predict the possible detection significance at various signal parameters. It is shown that the crucial parameter is the eective signal-to-noise ratio - the expected depth of the transit divided by the standard deviation of the measured photometric average within the transit. When this parameter exceeds the value of 6 we can expect a significant detection of the transit. We show that the box-fitting algorithm performs better than other methods available in the astronomical literature, especially for low signal-to-noise ratios.

Nested linear/lattice codes for structured multiterminal binning

Abstract: Network information theory promises high gains over simple point-to-point communication techniques, at the cost of higher complexity. However, lack of structured coding schemes limited the practical application of these concepts so far. One of the basic elements of a network code is the binning scheme. Wyner (1974, 1978) and other researchers proposed various forms of coset codes for efficient binning, yet these schemes were applicable only for lossless source (or noiseless channel) network coding. To extend the algebraic binning approach to lossy source (or noisy channel) network coding, previous work proposed the idea of nested codes, or more specifically, nested parity-check codes for the binary case and nested lattices in the continuous case. These ideas connect network information theory with the rich areas of linear codes and lattice codes, and have strong potential for practical applications. We review these developments and explore their tight relation to concepts such as combined shaping and precoding, coding for memories with defects, and digital watermarking. We also propose a few novel applications adhering to a unified approach.

Discovering statistically significant biclusters in gene expression data.

Abstract: In gene expression data, a bicluster is a subset of the genes exhibiting consistent patterns over a subset of the conditions We propose a new method to detect significant biclusters in large expression datasets Our approach is graph theoretic coupled with statistical modelling of the data Under plausible assumptions, our algorithm is polynomial and is guaranteed to find the most significant biclusters We tested our method on a collection of yeast expression profiles and on a human cancer dataset Cross validation results show high specificity in assigning function to genes based on their biclusters, and we are able to annotate in this way 196 uncharacterized yeast genes We also demonstrate how the biclusters lead to detecting new concrete biological associations In cancer data we are able to detect and relate finer tissue types than was previously possible We also show that the method outperforms the biclustering algorithm of Cheng and Church (2000)

Integration versus Outsourcing in Industry Equilibrium

Abstract: We develop an equilibrium model of industrial structure in which the organization of e rms is endogenous. Differentiated consumer products can be produced either by vertically integrated e rms or by pairs of specialized companies. Production of each variety of consumer good requires a specialized component. Vertically integrated e rms can manufacture the components they need, but they face a relatively high cost of governance. Specialized e rms can produce at lower cost, but search for partners is costly, and input suppliers face a potential holdup problem. We study the determinants of the equilibrium mode of organization when inputs are fully or partially specialized. I. INTRODUCTION

An improved stabilization method for linear time-delay systems

Abstract: In this paper, we combine a new approach for linear time delay systems based on a descriptor representation with a recent result on bounding of cross products of vectors. A delay-dependent criterion for determining the stability of systems with time-varying delays is obtained. This criterion is used to derive an efficient stabilizing state-feedback design method for systems with parameter uncertainty, of either the polytopic or the norm-bounded types.

Global air pollution crossroads over the Mediterranean

Abstract: The Mediterranean Intensive Oxidant Study, performed in the summer of 2001, uncovered air pollution layers from the surface to an altitude of 15 kilometers. In the boundary layer, air pollution standards are exceeded throughout the region, caused by West and East European pollution from the north. Aerosol particles also reduce solar radiation penetration to the surface, which can suppress precipitation. In the middle troposphere, Asian and to a lesser extent North American pollution is transported from the west. Additional Asian pollution from the east, transported from the monsoon in the upper troposphere, crosses the Mediterranean tropopause, which pollutes the lower stratosphere at middle latitudes.

A descriptor system approach to H/sub /spl infin// control of linear time-delay systems

Abstract: The output-feedback H/sub /spl infin// control problem is solved for continuous-time, linear, retarded and neutral-type systems. A delay-dependent solution is obtained in terms of linear matrix inequalities (LMIs) by using a descriptor model transformation of the system and by applying P. Park's inequality (1999) for bounding cross-terms. A state-feedback solution is derived for systems with polytopic parameter uncertainties. An output-feedback controller is then found by solving two LMIs, one of which is associated with a descriptor time-delay "innovation filter". The cases of instantaneous and delayed measurements are considered. Numerical examples are given which illustrate the effectiveness of the new theory.

A box-fitting algorithm in the search for periodic transits

Abstract: We study the statistical characteristics of a box-fitting algorithm to analyze stellar photometric time series in the search for periodic transits by extrasolar planets. The algorithm searches for signals characterized by a periodic alternation between two discrete levels, with much less time spent at the lower level. We present numerical as well as analytical results to predict the possible detection significance at various signal parameters. It is shown that the crucial parameter is the effective signal-to-noise ratio -- the expected depth of the transit divided by the standard deviation of the measured photometric average within the transit. When this parameter exceeds the value of 6 we can expect a significant detection of the transit. We show that the box-fitting algorithm performs better than other methods available in the astronomical literature, especially for low signal-to-noise ratios.

A Highly Significant Association between a COMT Haplotype and Schizophrenia

Abstract: Several lines of evidence have placed the catechol-O-methyltransferase (COMT) gene in the limelight as a candidate gene for schizophrenia. One of these is its biochemical function in metabolism of catecholamine neurotransmitters; another is the microdeletion, on chromosome 22q11, that includes the COMT gene and causes velocardiofacial syndrome, a syndrome associated with a high rate of psychosis, particularly schizophrenia. The interest in the COMT gene as a candidate risk factor for schizophrenia has led to numerous linkage and association analyses. These, however, have failed to produce any conclusive result. Here we report an efficient approach to gene discovery. The approach consists of ( i ) a large sample size—to our knowledge, the present study is the largest case-control study performed to date in schizophrenia; ( ii ) the use of Ashkenazi Jews, a well defined homogeneous population; and ( iii ) a stepwise procedure in which several single nucleotide polymorphisms (SNPs) are scanned in DNA pools, followed by individual genotyping and haplotype analysis of the relevant SNPs. We found a highly significant association between schizophrenia and a COMT haplotype ( P =9.5×10 −8 ). The approach presented can be widely implemented for the genetic dissection of other common diseases.

Sleep, neurobehavioral functioning, and behavior problems in school-age children

Abstract: The aim of this study was to examine the associations between sleep and neurobehavioral functioning (NBF) in school-age children. These variables were assessed for 135 unreferred, healthy school children (69 boys and 66 girls), from second-, fourth-, and sixth-grade classes. Objective assessment methods were used on the participants in their regular home settings. Sleep was monitored using actigraphy for 5 consecutive nights; and NBF was assessed using a computerized neurobehavioral evaluation system, administered twice, at different times of the day. Significant correlations between sleep-quality measures and NBF measures were found, particularly in the younger age group. Children with fragmented sleep were characterized by lower performance on NBF measures, particularly those associated with more complex tasks such as a continuous performance test and a symbol-digit substitution test. These children also had higher rates of behavior problems as reported by their parents on the Child Behavior Checklist. These results highlight the association between sleep quality, NBF, and behavior regulation in child development; and raise important questions about the origins of these associations and their developmental and clinical significance.

Efficient Unbound Docking of Rigid Molecules

Abstract: We present a new algorithm for unbound (real life) docking of molecules, whether protein-protein or protein-drug. The algorithm carries out rigid docking, with surface variability/flexibility implicitly addressed through liberal intermolecular penetration. The high efficiency of the algorithm is the outcome of several factors: (i) focusing initial molecular surface fitting on localized, curvature based surface patches; (ii) use of Geometric Hashing and Pose Clustering for initial transformation detection; (iii) accurate computation of shape complementarity utilizing the Distance Transform; (iv) efficient steric clash detection and geometric fit scoring based on a multi-resolution shape representation; and (v) utilization of biological information by focusing on hot spot rich surface patches. The algorithm has been implemented and applied to a large number of cases.

Calmodulins and Calcineurin B–like Proteins: Calcium Sensors for Specific Signal Response Coupling in Plants

Abstract: ### Calcium Signaling and Calcium Sensors: A General Paradigm Many extracellular signals, including light, biotic, and abiotic stress factors, elicit changes in cellular Ca2+ concentration in plants ([Trewavas and Knight, 1994][1]; [Bush, 1995][2]; [Braam et al., 1997][3]; [McAinsh et al., 1997][4

Complex fuzzy sets

Abstract: The objective of this paper is to investigate the innovative concept of complex fuzzy sets. The novelty of the complex fuzzy set lies in the range of values its membership function may attain. In contrast to a traditional fuzzy membership function, this range is not limited to [0, 1], but extended to the unit circle in the complex plane. Thus, the complex fuzzy set provides a mathematical framework for describing membership in a set in terms of a complex number. The inherent difficulty in acquiring intuition for the concept of complex-valued membership presents a significant obstacle to the realization of its full potential. Consequently, a major part of this work is dedicated to a discussion of the intuitive interpretation of complex-valued grades of membership. Examples of possible applications, which demonstrate the new concept, include a complex fuzzy representation of solar activity (via measurements of the sunspot number), and a signal processing application. A comprehensive study of the mathematical properties of the complex fuzzy set is presented. Basic set theoretic operations on complex fuzzy sets, such as complex fuzzy complement, union, and intersection, are discussed at length. Two novel operations, namely set rotation and set reflection, are introduced. Complex fuzzy relations are also considered. Index Terms-Complex fuzzy intersection, complex fuzzy relations, complex fuzzy sets, complex fuzzy union, complex-valued grades of membership, fuzzy complex numbers.

Rate4Site: an algorithmic tool for the identification of functional regions in proteins by surface mapping of evolutionary determinants within their homologues

Abstract: Motivation: A number of proteins of known threedimensional (3D) structure exist, with yet unknown function. In light of the recent progress in structure determination methodology, this number is likely to increase rapidly. A novel method is presented here: ‘Rate4Site’, which maps the rate of evolution among homologous proteins onto the molecular surface of one of the homologues whose 3D-structure is known. Functionally important regions often correspond to surface patches of slowly evolving residues. Results: Rate4Site estimates the rate of evolution of amino acid sites using the maximum likelihood (ML) principle. The ML estimate of the rates considers the topology and branch lengths of the phylogenetic tree, as well as the underlying stochastic process. To demonstrate its potency, we study the Src SH2 domain. Like previously established methods, Rate4Site detected the SH2 peptide-binding groove. Interestingly, it also detected inter-domain interactions between the SH2 domain and the rest of the Src protein that other methods failed to detect. Availability: Rate4Site can be downloaded at: http:// ashtoret.tau.ac.il/. It is implemented as a web server at:

Antioxidant therapy in acute central nervous system injury: current state

Abstract: Free radicals are highly reactive molecules generated predominantly during cellular respiration and normal metabolism. Imbalance between cellular production of free radicals and the ability of cells to defend against them is referred to as oxidative stress (OS). OS has been implicated as a potential contributor to the pathogenesis of acute central nervous system (CNS) injury. After brain injury by ischemic or hemorrhagic stroke or trauma, the production of reactive oxygen species (ROS) may increase, sometimes drastically, leading to tissue damage via several different cellular molecular pathways. Radicals can cause damage to cardinal cellular components such as lipids, proteins, and nucleic acids (e.g., DNA), leading to subsequent cell death by modes of necrosis or apoptosis. The damage can become more widespread due to weakened cellular antioxidant defense systems. Moreover, acute brain injury increases the levels of excitotoxic amino acids (such as glutamate), which also produce ROS, thereby promoting parenchymatous destruction. Therefore, treatment with antioxidants may theoretically act to prevent propagation of tissue damage and improve both the survival and neurological outcome. Several such agents of widely varying chemical structures have been investigated as therapeutic agents for acute CNS injury. Although a few of the antioxidants showed some efficacy in animal models or in small clinical studies, these findings have not been supported in comprehensive, controlled trials in patients. Reasons for these equivocal results may include, in part, inappropriate timing of administration or suboptimal drug levels at the target site in CNS. Better understanding of the pathological mechanisms of acute CNS injury would characterize the exact primary targets for drug intervention. Improved antioxidant design should take into consideration the relevant and specific harmful free radical, blood brain barrier (BBB) permeability, dose, and time administration. Novel combinations of drugs providing protection against various types injuries will probably exploit the potential synergistic effects of antioxidants in stroke.

AAA-ATPase p97/Cdc48p, a Cytosolic Chaperone Required for Endoplasmic Reticulum-Associated Protein Degradation

Abstract: Endoplasmic reticulum-associated degradation (ERAD) disposes of aberrant proteins in the secretory pathway. Protein substrates of ERAD are dislocated via the Sec61p translocon from the endoplasmic reticulum to the cytosol, where they are ubiquitinated and degraded by the proteasome. Since the Sec61p channel is also responsible for import of nascent proteins, this bidirectional passage should be coordinated, probably by molecular chaperones. Here we implicate the cytosolic chaperone AAA-ATPase p97/Cdc48p in ERAD. We show the association of mammalian p97 and its yeast homologue Cdc48p in complexes with two respective ERAD substrates, secretory immunoglobulin M in B lymphocytes and 6myc-Hmg2p in yeast. The membrane 6myc-Hmg2p as well as soluble lumenal CPY*, two short-lived ERAD substrates, are markedly stabilized in conditional cdc48 yeast mutants. The involvement of Cdc48p in dislocation is underscored by the accumulation of ERAD substrates in the endoplasmic reticulum when Cdc48p fails to function, as monitored by activation of the unfolded protein response. We propose that the role of p97/Cdc48p in ERAD, provided by its potential unfoldase activity and multiubiquitin binding capacity, is to act at the cytosolic face of the endoplasmic reticulum and to chaperone dislocation of ERAD substrates and present them to the proteasome.

Being Israeli: The Dynamics of Multiple Citizenship

Abstract: 1. Introduction Part I. Fragmented Citizenship in a Colonial Frontier Society: 2. The virtues of Ashkenazi pioneering 3. Mizrachim and women: between quality and quantity 4. The frontier within: Palestinians as second-class citizens 5. The wages of legitimation: Zionist and non-Zionist Orthodox Jews Part II. The Frontier Reopens: 6. New day on the frontier 7. The frontier erupts: the Intitfadas Part III. The Emergence of Civil Society: 8. Agents of political change 9. Economic liberalization and peacemaking 10. The 'Constitutional Revolution' 11. Shrinking social rights 12. Emergent citizenship groups? Immigrants from the FSU and Ethiopia and overseas foreign workers 13. Conclusion.

CD4 T Cell Depletion Is Linked Directly to Immune Activation in the Pathogenesis of HIV-1 and HIV-2 but Only Indirectly to the Viral Load

Abstract: The causal relationships among CD4 cell depletion, HIV replication, and immune activation are not well understood. HIV-2 infection, "nature's experiment" with inherently attenuated HIV disease, provides additional insights into this issue. We report the finding that in HIV-2 and HIV-1 patients with a comparable degree of CD4 depletion the imbalance in the relative sizes of the naive and memory T cell populations and the up-regulation of CD4 and CD8 cell activation markers (HLA-DR, CD38, CD69, Fas molecules) are similar, even though the viral load in the plasma of HIV-2-infected patients is two orders of magnitude lower than in HIV-1 patients and HIV-2 patients are known to have slower rates of CD4 T cell decline and a better clinical prognosis. Moreover, we found a similar increase in the frequency of cycling CD4 T cells (Ki67+), which was in strong correlation with the expression of activation markers. Finally, the level of T cell anergy, as assessed by the proliferative responses to CD3 stimulation and to a panel of microbial Ags, proved to be comparable in HIV-1 and HIV-2 patients with a similar degree of CD4 depletion despite large differences in viral load. Our data are consistent with a direct causal relationship between immune activation and CD4 cell depletion in HIV disease and an only indirect relation of these parameters to the virus replication rate. Invoking the concept of proximal immune activation and virus transmission, which links efficient transmission of virus to local cell activation and proliferation in response to Ags and inflammation, we propose an integrative interpretation of the data and suggest that strongly elevated immune activation induces CD4 cell depletion and not vice versa, with potential implications for the choice of treatment strategies.

Reachability and distance queries via 2-hop labels

Abstract: Reachability and distance queries in graphs are fundamental to numerous applications, ranging from geographic navigation systems to Internet routing Some of these applications involve huge graphs and yet require fast query answering We propose a new data structure for representing all distances in a graph The data structure is distributed in the sense that it may be viewed as assigning labels to the vertices, such that a query involving vertices u and v may be answered using only the labels of u and vOur labels are based on 2-hop covers of the shortest paths, or of all paths, in a graph For shortest paths, such a cover is a collection S of shortest paths such that for every two vertices u and v, there is a shortest path from u to v that is a concatenation of two paths from S We describe an efficient algorithm for finding an almost optimal 2-hop cover of a given collection of paths Our approach is general and can be applied to directed or undirected graphs, exact or approximate shortest paths, or to reachability queriesWe study the proposed data structure using a combination of theoretical and experimental means We implemented our algorithm and checked the size of the resulting data structure on several real-life networks from different application areas Our experiments show that the total size of the labels is typically not much larger than the network itself, and is usually considerably smaller than an explicit representation of the transitive closure of the network