Showing papers by "Technion – Israel Institute of Technology published in 2011"

International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases

Abstract: A Panel of International Experts was convened by the Infectious Diseases Society of America (IDSA) in collaboration with the European Society for Microbiology and Infectious Diseases (ESCMID) to update the 1999 Uncomplicated Urinary Tract Infection Guidelines by the IDSA. Co-sponsoring organizations include the American Congress of Obstetricians and Gynecologists, American Urological Association, Association of Medical Microbiology and Infectious Diseases-Canada, and the Society for Academic Emergency Medicine. The focus of this work is treatment of women with acute uncomplicated cystitis and pyelonephritis, diagnoses limited in these guidelines to premenopausal, non-pregnant women with no known urological abnormalities or co-morbidities. The issues of in vitro resistance prevalence and the ecological adverse effects of antimicrobial therapy (collateral damage) were considered as important factors in making optimal treatment choices and thus are reflected in the rankings of recommendations.

Structured Compressed Sensing: From Theory to Applications

Abstract: Compressed sensing (CS) is an emerging field that has attracted considerable research interest over the past few years. Previous review articles in CS limit their scope to standard discrete-to-discrete measurement architectures using matrices of randomized nature and signal models based on standard sparsity. In recent years, CS has worked its way into several new application areas. This, in turn, necessitates a fresh look on many of the basics of CS. The random matrix measurement operator must be replaced by more structured sensing architectures that correspond to the characteristics of feasible acquisition hardware. The standard sparsity prior has to be extended to include a much richer class of signals and to encode broader data models, including continuous-time signals. In our overview, the theme is exploiting signal and measurement structure in compressive sensing. The prime focus is bridging theory and practice; that is, to pinpoint the potential of structured CS strategies to emerge from the math to the hardware. Our summary highlights new directions as well as relations to more traditional CS, with the hope of serving both as a review to practitioners wanting to join this emerging field, and as a reference for researchers that attempts to put some of the existing ideas in perspective of practical applications.

Modelling the long QT syndrome with induced pluripotent stem cells

Abstract: The ability to generate patient-specific human induced pluripotent stem cells (iPSCs) offers a new paradigm for modelling human disease and for individualizing drug testing. Congenital long QT syndrome (LQTS) is a familial arrhythmogenic syndrome characterized by abnormal ion channel function and sudden cardiac death. Here we report the development of a patient/disease-specific human iPSC line from a patient with type-2 LQTS (which is due to the A614V missense mutation in the KCNH2 gene). The generated iPSCs were coaxed to differentiate into the cardiac lineage. Detailed whole-cell patch-clamp and extracellular multielectrode recordings revealed significant prolongation of the action-potential duration in LQTS human iPSC-derived cardiomyocytes (the characteristic LQTS phenotype) when compared to healthy control cells. Voltage-clamp studies confirmed that this action-potential-duration prolongation stems from a significant reduction of the cardiac potassium current I(Kr). Importantly, LQTS-derived cells also showed marked arrhythmogenicity, characterized by early-after depolarizations and triggered arrhythmias. We then used the LQTS human iPSC-derived cardiac-tissue model to evaluate the potency of existing and novel pharmacological agents that may either aggravate (potassium-channel blockers) or ameliorate (calcium-channel blockers, K(ATP)-channel openers and late sodium-channel blockers) the disease phenotype. Our study illustrates the ability of human iPSC technology to model the abnormal functional phenotype of an inherited cardiac disorder and to identify potential new therapeutic agents. As such, it represents a promising paradigm to study disease mechanisms, optimize patient care (personalized medicine), and aid in the development of new therapies.

Probing the photoelectrochemical properties of hematite (α-Fe2O3) electrodes using hydrogen peroxide as a hole scavenger

Abstract: We study hematite (α-Fe2O3) photoelectrodes for water splitting by examining the fate of photogenerated holes. Using H2O2 as an efficient hole scavenger, we collect all holes that arrive at the electrode/electrolyte interface. This provides the ability to distinguish between and quantify bulk and surface recombination processes involved in the photoelectrochemical oxidation of water. Below 1.0 VRHE, electrolyte oxidation kinetics limits the performance but above 1.2 VRHE bulk recombination becomes the limiting factor.

Non-Hermitian Quantum Mechanics

Abstract: Non-Hermitian quantum mechanics (NHQM) is an important alternative to the standard (Hermitian) formalism of quantum mechanics, enabling the solution of otherwise difficult problems. The first book to present this theory, it is useful to advanced graduate students and researchers in physics, chemistry and engineering. NHQM provides powerful numerical and analytical tools for the study of resonance phenomena - perhaps one of the most striking events in nature. It is especially useful for problems whose solutions cause extreme difficulties within the structure of a conventional Hermitian framework. NHQM has applications in a variety of fields, including optics, where the refractive index is complex; quantum field theory, where the parity-time (PT) symmetry properties of the Hamiltonian are investigated; and atomic and molecular physics and electrical engineering, where complex potentials are introduced to simplify numerical calculations.

Mesoscopic Physics of Electrons and Photons

Abstract: 1. Introduction: mesoscopic physics 2. Wave equations in random media 3. Perturbation theory 4. Probability of quantum diffusion 5. Properties of the diffusion equation 6. Dephasing 7. Electronic transport 8. Coherent backscattering of light 9. Diffusing wave spectroscopy 10. Spectral properties of disordered metals 11. Universal conductance fluctuations 12. Correlations of speckle patterns 13. Interactions and diffusion 14. Orbital magnetism and persistent currents 15. Formulary Index.

Trichoderma : the genomics of opportunistic success

Abstract: Trichoderma is a genus of common filamentous fungi that display a remarkable range of lifestyles and interactions with other fungi, animals and plants. Because of their ability to antagonize plant-pathogenic fungi and to stimulate plant growth and defence responses, some Trichoderma strains are used for biological control of plant diseases. In this Review, we discuss recent advances in molecular ecology and genomics which indicate that the interactions of Trichoderma spp. with animals and plants may have evolved as a result of saprotrophy on fungal biomass (mycotrophy) and various forms of parasitism on other fungi (mycoparasitism), combined with broad environmental opportunism.

Index Coding With Side Information

Abstract: Motivated by a problem of transmitting supplemental data over broadcast channels (Birk and Kol, INFOCOM 1998), we study the following coding problem: a sender communicates with n receivers R1,..., Rn. He holds an input x ∈ {0,01l}n and wishes to broadcast a single message so that each receiver Ri can recover the bit xi. Each Ri has prior side information about x, induced by a directed graph Grain nodes; Ri knows the bits of a; in the positions {j | (i,j) is an edge of G}.G is known to the sender and to the receivers. We call encoding schemes that achieve this goal INDEXcodes for {0,1}n with side information graph G. In this paper we identify a measure on graphs, the minrank, which exactly characterizes the minimum length of linear and certain types of nonlinear INDEX codes. We show that for natural classes of side information graphs, including directed acyclic graphs, perfect graphs, odd holes, and odd anti-holes, minrank is the optimal length of arbitrary INDEX codes. For arbitrary INDEX codes and arbitrary graphs, we obtain a lower bound in terms of the size of the maximum acyclic induced subgraph. This bound holds even for randomized codes, but has been shown not to be tight.

Comparative genome sequence analysis underscores mycoparasitism as the ancestral life style of Trichoderma

Abstract: Mycoparasitism, a lifestyle where one fungus is parasitic on another fungus, has special relevance when the prey is a plant pathogen, providing a strategy for biological control of pests for plant protection. Probably, the most studied biocontrol agents are species of the genus Hypocrea/Trichoderma. Here we report an analysis of the genome sequences of the two biocontrol species Trichoderma atroviride (teleomorph Hypocrea atroviridis) and Trichoderma virens (formerly Gliocladium virens, teleomorph Hypocrea virens), and a comparison with Trichoderma reesei (teleomorph Hypocrea jecorina). These three Trichoderma species display a remarkable conservation of gene order (78 to 96%), and a lack of active mobile elements probably due to repeat-induced point mutation. Several gene families are expanded in the two mycoparasitic species relative to T. reesei or other ascomycetes, and are overrepresented in non-syntenic genome regions. A phylogenetic analysis shows that T. reesei and T. virens are derived relative to T. atroviride. The mycoparasitism-specific genes thus arose in a common Trichoderma ancestor but were subsequently lost in T. reesei. The data offer a better understanding of mycoparasitism, and thus enforce the development of improved biocontrol strains for efficient and environmentally friendly protection of plants.

The Subgradient Extragradient Method for Solving Variational Inequalities in Hilbert Space.

Abstract: We present a subgradient extragradient method for solving variational inequalities in Hilbert space. In addition, we propose a modified version of our algorithm that finds a solution of a variational inequality which is also a fixed point of a given nonexpansive mapping. We establish weak convergence theorems for both algorithms.

Child health, developmental plasticity, and epigenetic programming.

Abstract: Plasticity in developmental programming has evolved in order to provide the best chances of survival and reproductive success to the organism under changing environments. Environmental conditions that are experienced in early life can profoundly influence human biology and long-term health. Developmental origins of health and disease and life-history transitions are purported to use placental, nutritional, and endocrine cues for setting long-term biological, mental, and behavioral strategies in response to local ecological and/or social conditions. The window of developmental plasticity extends from preconception to early childhood and involves epigenetic responses to environmental changes, which exert their effects during life-history phase transitions. These epigenetic responses influence development, cell- and tissue-specific gene expression, and sexual dimorphism, and, in exceptional cases, could be transmitted transgenerationally. Translational epigenetic research in child health is a reiterative process that ranges from research in the basic sciences, preclinical research, and pediatric clinical research. Identifying the epigenetic consequences of fetal programming creates potential applications in clinical practice: the development of epigenetic biomarkers for early diagnosis of disease, the ability to identify susceptible individuals at risk for adult diseases, and the development of novel preventive and curative measures that are based on diet and/or novel epigenetic drugs.

How to Construct Polar Codes

Abstract: A method for efficiently constructing polar codes is presented and analyzed. Although polar codes are explicitly defined, straightforward construction is intractable since the resulting polar bit-channels have an output alphabet that grows exponentially with he code length. Thus the core problem that needs to be solved is that of faithfully approximating a bit-channel with an intractably large alphabet by another channel having a manageable alphabet size. We devise two approximation methods which "sandwich" the original bit-channel between a degraded and an upgraded version thereof. Both approximations can be efficiently computed, and turn out to be extremely close in practice. We also provide theoretical analysis of our construction algorithms, proving that for any fixed $\epsilon > 0$ and all sufficiently large code lengths $n$, polar codes whose rate is within $\epsilon$ of channel capacity can be constructed in time and space that are both linear in $n$.

Experimental Observation of Optical Bound States in the Continuum

Abstract: We present the experimental observation of bound states in the continuum. Our experiments are carried out in an optical waveguide array structure, where the bound state (guided mode) is decoupled from the continuum by virtue of symmetry only. We demonstrate that breaking the symmetry of the system couples this special bound state to continuum states, leading to radiative losses. These experiments demonstrate ideas initially proposed by von Neumann and Wigner in 1929 and offer new possibilities for integrated optical elements and analogous realizations with cold atoms and optical trapping of particles.

Review article: loss of response to anti‐TNF treatments in Crohn’s disease

Abstract: Aliment Pharmacol Ther 2011; 33: 987–995 Summary Background Loss of response to anti-TNF agents in Crohn’s disease is an emerging clinical problem. Aim To review the causes, incidence and management approach of loss of response. Methods A search of medical database (PubMed) and of meetings’ proceedings for definitions, causes and incidence of loss of response was carried out. Personal correspondence with principal investigators was conducted to retrieve missing data. Results Various definitions of loss of response abound, hampering the ability to assess accurately the magnitude and management of this clinical problem. We propose to distinguish between a clinical worsening on anti-TNF treatment and a true loss of response to anti-TNFs. Accordingly, loss of response to anti-TNFs at 12 months of therapy occurs in 23–46% of patients when judged by dose intensification, or 5–13% when gauged by drug discontinuation rates. The management of loss of response should allow for a period of watchful waiting as quite often the patients’ symptoms may resolve without alteration of therapy. If they do not, then identifying the correct mechanism responsible for clinical deterioration is prudent. Once symptoms are ascertained to arise from inflammatory IBD activity, drug level and antidrug antibody measurement can then help distinguish between non-adherence to therapy, immunogenicity and non-immune clearance of anti-TNF, or an un-chequered inflammation despite adequate anti-TNF levels. The latter finding may be best addressed by a switch to another class of immunomodulators, whereas a low drug level should probably be managed by dose intensification or a switch to another anti-TNF. Conclusion Studies defining how best to translate drug-level monitoring and other mechanistic considerations into clinical decisions are urgently needed.

A word at a time: computing word relatedness using temporal semantic analysis

Abstract: Computing the degree of semantic relatedness of words is a key functionality of many language applications such as search, clustering, and disambiguation. Previous approaches to computing semantic relatedness mostly used static language resources, while essentially ignoring their temporal aspects. We believe that a considerable amount of relatedness information can also be found in studying patterns of word usage over time. Consider, for instance, a newspaper archive spanning many years. Two words such as "war" and "peace" might rarely co-occur in the same articles, yet their patterns of use over time might be similar. In this paper, we propose a new semantic relatedness model, Temporal Semantic Analysis (TSA), which captures this temporal information. The previous state of the art method, Explicit Semantic Analysis (ESA), represented word semantics as a vector of concepts. TSA uses a more refined representation, where each concept is no longer scalar, but is instead represented as time series over a corpus of temporally-ordered documents. To the best of our knowledge, this is the first attempt to incorporate temporal evidence into models of semantic relatedness. Empirical evaluation shows that TSA provides consistent improvements over the state of the art ESA results on multiple benchmarks.

Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase

Abstract: Fumarate hydratase (FH) is an enzyme of the tricarboxylic acid cycle (TCA cycle) that catalyses the hydration of fumarate into malate. Germline mutations of FH are responsible for hereditary leiomyomatosis and renal-cell cancer (HLRCC). It has previously been demonstrated that the absence of FH leads to the accumulation of fumarate, which activates hypoxia-inducible factors (HIFs) at normal oxygen tensions. However, so far no mechanism that explains the ability of cells to survive without a functional TCA cycle has been provided. Here we use newly characterized genetically modified kidney mouse cells in which Fh1 has been deleted, and apply a newly developed computer model of the metabolism of these cells to predict and experimentally validate a linear metabolic pathway beginning with glutamine uptake and ending with bilirubin excretion from Fh1-deficient cells. This pathway, which involves the biosynthesis and degradation of haem, enables Fh1-deficient cells to use the accumulated TCA cycle metabolites and permits partial mitochondrial NADH production. We predicted and confirmed that targeting this pathway would render Fh1-deficient cells non-viable, while sparing wild-type Fh1-containing cells. This work goes beyond identifying a metabolic pathway that is induced in Fh1-deficient cells to demonstrate that inhibition of haem oxygenation is synthetically lethal when combined with Fh1 deficiency, providing a new potential target for treating HLRCC patients.

Predicting selective drug targets in cancer through metabolic networks

Abstract: The interest in studying metabolic alterations in cancer and their potential role as novel targets for therapy has been rejuvenated in recent years. Here, we report the development of the first genome-scale network model of cancer metabolism, validated by correctly identifying genes essential for cellular proliferation in cancer cell lines. The model predicts 52 cytostatic drug targets, of which 40% are targeted by known, approved or experimental anticancer drugs, and the rest are new. It further predicts combinations of synthetic lethal drug targets, whose synergy is validated using available drug efficacy and gene expression measurements across the NCI-60 cancer cell line collection. Finally, potential selective treatments for specific cancers that depend on cancer type-specific downregulation of gene expression and somatic mutations are compiled.

Charged-particle multiplicities in pp interactions measured with the ATLAS detector at the LHC

Abstract: Measurements are presented from proton-proton collisions at centre-of-mass energies of root s = 0.9, 2.36 and 7 TeV recorded with the ATLAS detector at the LHC. Events were collected using a single-arm minimum-bias trigger. The charged-particle multiplicity, its dependence on transverse momentum and pseudorapidity and the relationship between the mean transverse momentum and charged-particle multiplicity are measured. Measurements in different regions of phase space are shown, providing diffraction-reduced measurements as well as more inclusive ones. The observed distributions are corrected to well-defined phase-space regions, using model-independent corrections. The results are compared to each other and to various Monte Carlo (MC) models, including a new AMBT1 pythia6 tune. In all the kinematic regions considered, the particle multiplicities are higher than predicted by the MC models. The central charged-particle multiplicity per event and unit of pseudorapidity, for tracks with p(T) > 100 MeV, is measured to be 3.483 +/- 0.009 (stat) +/- 0.106 (syst) at root s = 0.9 TeV and 5.630 +/- 0.003 (stat) +/- 0.169 (syst) at root s = 7 TeV.

Intramembrane cavitation as a unifying mechanism for ultrasound-induced bioeffects.

Abstract: The purpose of this study was to develop a unified model capable of explaining the mechanisms of interaction of ultrasound and biological tissue at both the diagnostic nonthermal, noncavitational ( 100 mW·cm−2) spatial peak temporal average intensity levels. The cellular-level model (termed “bilayer sonophore”) combines the physics of bubble dynamics with cell biomechanics to determine the dynamic behavior of the two lipid bilayer membrane leaflets. The existence of such a unified model could potentially pave the way to a number of controlled ultrasound-assisted applications, including CNS modulation and blood–brain barrier permeabilization. The model predicts that the cellular membrane is intrinsically capable of absorbing mechanical energy from the ultrasound field and transforming it into expansions and contractions of the intramembrane space. It further predicts that the maximum area strain is proportional to the acoustic pressure amplitude and inversely proportional to the square root of the frequency () and is intensified by proximity to free surfaces, the presence of nearby microbubbles in free medium, and the flexibility of the surrounding tissue. Model predictions were experimentally supported using transmission electron microscopy (TEM) of multilayered live-cell goldfish epidermis exposed in vivo to continuous wave (CW) ultrasound at cavitational (1 MHz) and noncavitational (3 MHz) conditions. Our results support the hypothesis that ultrasonically induced bilayer membrane motion, which does not require preexistence of air voids in the tissue, may account for a variety of bioeffects and could elucidate mechanisms of ultrasound interaction with biological tissue that are currently not fully understood.

Xampling: Analog to digital at sub-Nyquist rates

Abstract: The authors present a sub-Nyquist analog-to-digital converter of wideband inputs. The circuit realises the recently proposed modulated wideband converter, which is a flexible platform for sampling signals according to their actual bandwidth occupation. The theoretical work enables, for example, a sub-Nyquist wideband communication receiver, which has no prior information on the transmitter carrier positions. The present design supports input signals with 2 GHz Nyquist rate and 120 MHz spectrum occupancy, with arbitrary transmission frequencies. The sampling rate is as low as 280 MHz. To the best of the authors' knowledge, this is the first reported hardware that performs sub-Nyquist sampling and reconstruction of wideband signals. The authors describe the various circuit design considerations, with an emphasis on the non-ordinary challenges the converter introduces: mixing a signal with a multiple set of sinusoids, rather than a single local oscillator, and generation of highly transient periodic waveforms, with transient intervals on the order of the Nyquist rate. Hardware experiments validate the design and demonstrate sub-Nyquist sampling and signal reconstruction.

Engineering the Growth Factor Microenvironment with Fibronectin Domains to Promote Wound and Bone Tissue Healing

Abstract: Although growth factors naturally exert their morphogenetic influences within the context of the extracellular matrix microenvironment, the interactions among growth factors, their receptors, and other extracellular matrix components are typically ignored in clinical delivery of growth factors. We present an approach for engineering the cellular microenvironment to greatly accentuate the effects of vascular endothelial growth factor-A (VEGF-A) and platelet-derived growth factor-BB (PDGF-BB) for skin repair, and of bone morphogenetic protein-2 (BMP-2) and PDGF-BB for bone repair. A multifunctional recombinant fragment of fibronectin (FN) was engineered to comprise (i) a factor XIIIa substrate fibrin-binding sequence, (ii) the 9th to 10th type III FN repeat (FN III9-10) containing the major integrin-binding domain, and (iii) the 12th to 14th type III FN repeat (FN III12-14), which binds growth factors promiscuously, including VEGF-A165, PDGF-BB, and BMP-2. We show potent synergistic signaling and morphogenesis between α5β1 integrin and the growth factor receptors, but only when FN III9-10 and FN III12-14 are proximally presented in the same polypeptide chain (FN III9-10/12-14). The multifunctional FN III9-10/12-14 greatly enhanced the regenerative effects of the growth factors in vivo in a diabetic mouse model of chronic wounds (primarily through an angiogenic mechanism) and in a rat model of critical-size bone defects (through a mesenchymal stem cell recruitment mechanism) at doses where the growth factors delivered within fibrin only had no significant effects.

Balance Within and Across Domains: The Performance Implications of Exploration and Exploitation in Alliances

Abstract: Organizational research advocates that firms balance exploration and exploitation, yet it acknowledges inherent challenges in reconciling these opposing activities. To overcome these challenges, such research suggests that firms establish organizational separation between exploring and exploiting units or engage in temporal separation whereby they oscillate between exploration and exploitation over time. Nevertheless, these approaches entail resource allocation trade-offs and conflicting organizational routines, which may undermine organizational performance as firms seek to balance exploration and exploitation within a discrete field of organizational activity (i.e., domain). We posit that firms can overcome such impediments and enhance their performance if they explore in one domain while exploiting in another. Studying the alliance portfolios of software firms, we demonstrate that firms do not typically benefit from balancing exploration and exploitation within the function domain (technology versus marketing and production alliances) and structure domain (new versus prior partners). Nevertheless, firms that balance exploration and exploitation across these domains by engaging in research and development alliances while collaborating with their prior partners, or alternatively, by forming marketing and production alliances while seeking new partners, gain in profits and market value. Moreover, we reveal that increases in firm size that exacerbate resource allocation trade-offs and routine rigidity reinforce the benefits of balance across domains and the costs of balance within domains. Our domain separation approach offers new insights into how firms can benefit from balancing exploration and exploitation. What matters is not simply whether firms balance exploration and exploitation in their alliance formation decisions but the means by which they achieve such balance.