Showing papers by "Tel Aviv University published in 2009"

GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists

Abstract: Since the inception of the GO annotation project, a variety of tools have been developed that support exploring and searching the GO database In particular, a variety of tools that perform GO enrichment analysis are currently available Most of these tools require as input a target set of genes and a background set and seek enrichment in the target set compared to the background set A few tools also exist that support analyzing ranked lists The latter typically rely on simulations or on union-bound correction for assigning statistical significance to the results GOrilla is a web-based application that identifies enriched GO terms in ranked lists of genes, without requiring the user to provide explicit target and background sets This is particularly useful in many typical cases where genomic data may be naturally represented as a ranked list of genes (eg by level of expression or of differential expression) GOrilla employs a flexible threshold statistical approach to discover GO terms that are significantly enriched at the top of a ranked gene list Building on a complete theoretical characterization of the underlying distribution, called mHG, GOrilla computes an exact p-value for the observed enrichment, taking threshold multiple testing into account without the need for simulations This enables rigorous statistical analysis of thousand of genes and thousands of GO terms in order of seconds The output of the enrichment analysis is visualized as a hierarchical structure, providing a clear view of the relations between enriched GO terms GOrilla is an efficient GO analysis tool with unique features that make a useful addition to the existing repertoire of GO enrichment tools GOrilla's unique features and advantages over other threshold free enrichment tools include rigorous statistics, fast running time and an effective graphical representation GOrilla is publicly available at: http://cbl-gorillacstechnionacil

Fast Gradient-Based Algorithms for Constrained Total Variation Image Denoising and Deblurring Problems

Abstract: This paper studies gradient-based schemes for image denoising and deblurring problems based on the discretized total variation (TV) minimization model with constraints. We derive a fast algorithm for the constrained TV-based image deburring problem. To achieve this task, we combine an acceleration of the well known dual approach to the denoising problem with a novel monotone version of a fast iterative shrinkage/thresholding algorithm (FISTA) we have recently introduced. The resulting gradient-based algorithm shares a remarkable simplicity together with a proven global rate of convergence which is significantly better than currently known gradient projections-based methods. Our results are applicable to both the anisotropic and isotropic discretized TV functionals. Initial numerical results demonstrate the viability and efficiency of the proposed algorithms on image deblurring problems with box constraints.

The role of dynamic conformational ensembles in biomolecular recognition

Abstract: Molecular recognition is central to all biological processes. For the past 50 years, Koshland's 'induced fit' hypothesis has been the textbook explanation for molecular recognition events. However, recent experimental evidence supports an alternative mechanism. 'Conformational selection' postulates that all protein conformations pre-exist, and the ligand selects the most favored conformation. Following binding the ensemble undergoes a population shift, redistributing the conformational states. Both conformational selection and induced fit appear to play roles. Following binding by a primary conformational selection event, optimization of side chain and backbone interactions is likely to proceed by an induced fit mechanism. Conformational selection has been observed for protein-ligand, protein-protein, protein-DNA, protein-RNA and RNA-ligand interactions. These data support a new molecular recognition paradigm for processes as diverse as signaling, catalysis, gene regulation and protein aggregation in disease, which has the potential to significantly impact our views and strategies in drug design, biomolecular engineering and molecular evolution.

Multicenter Analysis of Glucocerebrosidase Mutations in Parkinson's Disease

Abstract: Background Recent studies indicate an increased frequency of mutations in the gene encoding glucocerebrosidase (GBA), a deficiency of which causes Gaucher's disease, among patients with Parkinson's disease. We aimed to ascertain the frequency of GBA mutations in an ethnically diverse group of patients with Parkinson's disease. Methods Sixteen centers participated in our international, collaborative study: five from the Americas, six from Europe, two from Israel, and three from Asia. Each center genotyped a standard DNA panel to permit comparison of the genotyping results across centers. Genotypes and phenotypic data from a total of 5691 patients with Parkinson's disease (780 Ashkenazi Jews) and 4898 controls (387 Ashkenazi Jews) were analyzed, with multivariate logistic-regression models and the Mantel–Haenszel procedure used to estimate odds ratios across centers. Results All 16 centers could detect two GBA mutations, L444P and N370S. Among Ashkenazi Jewish subjects, either mutation was found in 15% of p...

On lattices, learning with errors, random linear codes, and cryptography

Abstract: Our main result is a reduction from worst-case lattice problems such as GapSVP and SIVP to a certain learning problem. This learning problem is a natural extension of the “learning from parity with error” problem to higher moduli. It can also be viewed as the problem of decoding from a random linear code. This, we believe, gives a strong indication that these problems are hard. Our reduction, however, is quantum. Hence, an efficient solution to the learning problem implies a quantum algorithm for GapSVP and SIVP. A main open question is whether this reduction can be made classical (i.e., nonquantum).We also present a (classical) public-key cryptosystem whose security is based on the hardness of the learning problem. By the main result, its security is also based on the worst-case quantum hardness of GapSVP and SIVP. The new cryptosystem is much more efficient than previous lattice-based cryptosystems: the public key is of size O(n2) and encrypting a message increases its size by a factor of O(n) (in previous cryptosystems these values are O(n4) and O(n2), respectively). In fact, under the assumption that all parties share a random bit string of length O(n2), the size of the public key can be reduced to O(n).

Multi-class AdaBoost ∗

Abstract: Boosting has been a very successful technique for solving the two-class classification problem. In going from two-class to multi-class classification, most algorithms have been restricted to reducing the multi-class classification problem to multiple two-class problems. In this paper, we propose a new algorithm that naturally extends the original AdaBoost algorithm to the multiclass case without reducing it to multiple two-class problems. Similar to AdaBoost in the twoclass case, this new algorithm combines weak classifiers and only requires the performance of each weak classifier be better than random guessing (rather than 1/2). We further provide a statistical justification for the new algorithm using a novel multi-class exponential loss function and forward stage-wise additive modeling. As shown in the paper, the new algorithm is extremely easy to implement and is highly competitive with the best currently available multi-class classification methods.

Transgenerational epigenetic inheritance: prevalence, mechanisms, and implications for the study of heredity and evolution

Abstract: This review describes new developments in the study of transgenerational epigenetic inheritance, a component of epigenetics. We start by examining the basic concepts of the field and the mechanisms that underlie epigenetic inheritance. We present a comprehensive review of transgenerational cellular epigenetic inheritance among different taxa in the form of a table, and discuss the data contained therein. The analysis of these data shows that epigenetic inheritance is ubiquitous and suggests lines of research that go beyond present approaches to the subject. We conclude by exploring some of the consequences of epigenetic inheritance for the study of evolution, while also pointing to the importance of recognizing and understanding epigenetic inheritance for practical and theoretical issues in biology.

Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestans.

Abstract: Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement(1). To this day, it affects world agriculture by causing the most destructive disease of potato, the fourth largest food crop and a critical alternative to the major cereal crops for feeding the world's population(1). Current annual worldwide potato crop losses due to late blight are conservatively estimated at $6.7 billion(2). Management of this devastating pathogen is challenged by its remarkable speed of adaptation to control strategies such as genetically resistant cultivars(3,4). Here we report the sequence of the P. infestans genome, which at similar to 240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates. Its expansion results from a proliferation of repetitive DNA accounting for similar to 74% of the genome. Comparison with two other Phytophthora genomes showed rapid turnover and extensive expansion of specific families of secreted disease effector proteins, including many genes that are induced during infection or are predicted to have activities that alter host physiology. These fast-evolving effector genes are localized to highly dynamic and expanded regions of the P. infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.

THE SINS SURVEY: SINFONI INTEGRAL FIELD SPECTROSCOPY OF z ∼ 2 STAR-FORMING GALAXIES*

Abstract: We present the Spectroscopic Imaging survey in the near-infrared (near-IR) with SINFONI (SINS) of high-redshift galaxies. With 80 objects observed and 63 detected in at least one rest-frame optical nebular emission line, mainly Hα, SINS represents the largest survey of spatially resolved gas kinematics, morphologies, and physical properties of star-forming galaxies at z ~ 1-3. We describe the selection of the targets, the observations, and the data reduction. We then focus on the "SINS Hα sample," consisting of 62 rest-UV/optically selected sources at 1.3 < z < 2.6 for which we targeted primarily the Hα and [N II] emission lines. Only ≈30% of this sample had previous near-IR spectroscopic observations. The galaxies were drawn from various imaging surveys with different photometric criteria; as a whole, the SINS Hα sample covers a reasonable representation of massive M_* ≳ 10^(10) M_☉ star-forming galaxies at z ≈ 1.5-2.5, with some bias toward bluer systems compared to pure K-selected samples due to the requirement of secure optical redshift. The sample spans 2 orders of magnitude in stellar mass and in absolute and specific star formation rates, with median values ≈3 × 10^(10) M_☉, ≈70 M_☉ yr^(–1), and ≈3 Gyr^(–1). The ionized gas distribution and kinematics are spatially resolved on scales ranging from ≈1.5 kpc for adaptive optics assisted observations to typically ≈4-5 kpc for seeing-limited data. The Hα morphologies tend to be irregular and/or clumpy. About one-third of the SINS Hα sample galaxies are rotation-dominated yet turbulent disks, another one-third comprises compact and velocity dispersion-dominated objects, and the remaining galaxies are clear interacting/merging systems; the fraction of rotation-dominated systems increases among the more massive part of the sample. The Hα luminosities and equivalent widths suggest on average roughly twice higher dust attenuation toward the H II regions relative to the bulk of the stars, and comparable current and past-averaged star formation rates.

VTrack: accurate, energy-aware road traffic delay estimation using mobile phones

Abstract: Traffic delays and congestion are a major source of inefficiency, wasted fuel, and commuter frustration. Measuring and localizing these delays, and routing users around them, is an important step towards reducing the time people spend stuck in traffic. As others have noted, the proliferation of commodity smartphones that can provide location estimates using a variety of sensors---GPS, WiFi, and/or cellular triangulation---opens up the attractive possibility of using position samples from drivers' phones to monitor traffic delays at a fine spatiotemporal granularity. This paper presents VTrack, a system for travel time estimation using this sensor data that addresses two key challenges: energy consumption and sensor unreliability. While GPS provides highly accurate location estimates, it has several limitations: some phones don't have GPS at all, the GPS sensor doesn't work in "urban canyons" (tall buildings and tunnels) or when the phone is inside a pocket, and the GPS on many phones is power-hungry and drains the battery quickly. In these cases, VTrack can use alternative, less energy-hungry but noisier sensors like WiFi to estimate both a user's trajectory and travel time along the route. VTrack uses a hidden Markov model (HMM)-based map matching scheme and travel time estimation method that interpolates sparse data to identify the most probable road segments driven by the user and to attribute travel times to those segments. We present experimental results from real drive data and WiFi access point sightings gathered from a deployment on several cars. We show that VTrack can tolerate significant noise and outages in these location estimates, and still successfully identify delay-prone segments, and provide accurate enough delays for delay-aware routing algorithms. We also study the best sampling strategies for WiFi and GPS sensors for different energy cost regimes.

Donor-Derived Brain Tumor Following Neural Stem Cell Transplantation in an Ataxia Telangiectasia Patient

Abstract: Background Neural stem cells are currently being investigated as potential therapies for neurodegenerative diseases, stroke, and trauma. However, concerns have been raised over the safety of this experimental therapeutic approach, including, for example, whether there is the potential for tumors to develop from transplanted stem cells. Methods and Findings A boy with ataxia telangiectasia (AT) was treated with intracerebellar and intrathecal injection of human fetal neural stem cells. Four years after the first treatment he was diagnosed with a multifocal brain tumor. The biopsied tumor was diagnosed as a glioneuronal neoplasm. We compared the tumor cells and the patient's peripheral blood cells by fluorescent in situ hybridization using X and Y chromosome probes, by PCR for the amelogenin gene X- and Y-specific alleles, by MassArray for the ATM patient specific mutation and for several SNPs, by PCR for polymorphic microsatellites, and by human leukocyte antigen (HLA) typing. Molecular and cytogenetic studies showed that the tumor was of nonhost origin suggesting it was derived from the transplanted neural stem cells. Microsatellite and HLA analysis demonstrated that the tumor is derived from at least two donors. Conclusions This is the first report of a human brain tumor complicating neural stem cell therapy. The findings here suggest that neuronal stem/progenitor cells may be involved in gliomagenesis and provide the first example of a donor-derived brain tumor. Further work is urgently needed to assess the safety of these therapies.

A double-blind, delayed-start trial of rasagiline in Parkinson's disease.

Abstract: In this double-blind trial, we examined the possibility that rasagiline has diseasemodifying effects in Parkinson’s disease. A total of 1176 subjects with untreated Parkinson’s disease were randomly assigned to receive rasagiline (at a dose of either 1 mg or 2 mg per day) for 72 weeks (the early-start group) or placebo for 36 weeks followed by rasagiline (at a dose of either 1 mg or 2 mg per day) for 36 weeks (the delayed-start group). To determine a positive result with either dose, the early-start treatment group had to meet each of three hierarchical end points of the primary analysis based on the Unified Parkinson’s Disease Rating Scale (UPDRS, a 176-point scale, with higher numbers indicating more severe disease): superiority to placebo in the rate of change in the UPDRS score between weeks 12 and 36, superiority to delayed-start treatment in the change in the score between baseline and week 72, and noninferiority to delayed-start treatment in the rate of change in the score between weeks 48 and 72. Results Early-start treatment with rasagiline at a dose of 1 mg per day met all end points in the primary analysis: a smaller mean (±SE) increase (rate of worsening) in the UPDRS score between weeks 12 and 36 (0.09±0.02 points per week in the early-start group vs. 0.14±0.01 points per week in the placebo group, P = 0.01), less worsening in the score between baseline and week 72 (2.82±0.53 points in the early-start group vs. 4.52±0.56 points in the delayed-start group, P = 0.02), and noninferiority between the two groups with respect to the rate of change in the UPDRS score between weeks 48 and 72 (0.085±0.02 points per week in the early-start group vs. 0.085±0.02 points per week in the delayed-start group, P<0.001). All three end points were not met with rasagiline at a dose of 2 mg per day, since the change in the UPDRS score between baseline and week 72 was not significantly different in the two groups (3.47±0.50 points in the earlystart group and 3.11±0.50 points in the delayed-start group, P = 0.60). Conclusions Early treatment with rasagiline at a dose of 1 mg per day provided benefits that were consistent with a possible disease-modifying effect, but early treatment with rasagiline at a dose of 2 mg per day did not. Because the two doses were associated with different outcomes, the study results must be interpreted with caution. (ClinicalTrials. gov number, NCT00256204.)

Free water elimination and mapping from diffusion MRI.

Abstract: Relating brain tissue properties to diffusion tensor imaging (DTI) is limited when an image voxel contains partial volume of brain tissue with free water, such as cerebrospinal fluid or edema, rendering the DTI indices no longer useful for describing the underlying tissue properties. We propose here a method for separating diffusion properties of brain tissue from surrounding free water while mapping the free water volume. This is achieved by fitting a bi-tensor model for which a mathematical framework is introduced to stabilize the fitting. Applying the method on datasets from a healthy subject and a patient with edema yielded corrected DTI indices and a more complete tract reconstruction that passed next to the ventricles and through the edema. We were able to segment the edema into areas according to the condition of the underlying tissue. In addition, the volume of free water is suggested as a new quantitative contrast of diffusion MRI. The findings suggest that free water is not limited to the borders of the brain parenchyma; it therefore contributes to the architecture surrounding neuronal bundles and may indicate specific anatomical processes. The analysis requires a conventional DTI acquisition and can be easily merged with existing DTI pipelines.

Transiting exoplanets from the CoRoT space mission VIII. CoRoT-7b: the first Super-Earth with measured radius

Abstract: Aims. We report the discovery of very shallow (ΔF/F ≈ 3.4× 10 −4 ), periodic dips in the light curve of an active V = 11.7 G9V star observed by the CoRoT satellite, which we interpret as caused by a transiting companion. We describe the 3-colour CoRoT data and complementary ground-based observations that support the planetary nature of the companion. Methods. We used CoRoT colours information, good angular resolution ground-based photometric observations in- and out- of transit, adaptive optics imaging, near-infrared spectroscopy, and preliminary results from radial velocity measurements, to test the diluted eclipsing binary scenarios. The parameters of the host star were derived from optical spectra, which were then combined with the CoRoT light curve to derive parameters of the companion. Results. We examined all conceivable cases of false positives carefully, and all the tests support the planetary hypothesis. Blends with separation >0.40 �� or triple systems are almost excluded with a 8 × 10 −4 risk left. We conclude that, inasmuch we have been exhaustive, we have discovered a planetary companion, named CoRoT-7b, for which we derive a period of 0.853 59 ± 3 × 10 −5 day and a radius of Rp = 1.68 ± 0.09 REarth .A nalysis of preliminary radial velocity data yields an upper limit of 21 MEarth for the companion mass, supporting the finding. Conclusions. CoRoT-7b is very likely the first Super-Earth with a measured radius. This object illustrates what will probably become a common situation with missions such as Kepler, namely the need to establish the planetary origin of transits in the absence of a firm radial velocity detection and mass measurement. The composition of CoRoT-7b remains loosely constrained without a precise mass. A very high surface temperature on its irradiated face, ≈1800–2600 K at the substellar point, and a very low one, ≈50 K, on its dark face assuming no atmosphere, have been derived.

The Radius-Luminosity Relationship For Active Galactic Nuclei: The Effect of Host-Galaxy Starlight On Luminosity Measurements. II. The Full Sample of Reverberation-Mapped AGNs

Abstract: We present high-resolution Hubble Space Telescope images of all 35 active galactic nuclei (AGNs) with optical reverberation-mapping results, which we have modeled to create a nucleus-free image of each AGN host galaxy. From the nucleus-free images, we determine the host-galaxy contribution to ground-based spectroscopic luminosity measurements at 5100 A. After correcting the luminosities of the AGNs for the contribution from starlight, we re-examine the Hβ R BLR-L relationship. Our best fit for the relationship gives a power-law slope of 0.52 with a range of 0.45-0.59 allowed by the uncertainties. This is consistent with our previous findings, and thus still consistent with the naive assumption that all AGNs are simply luminosity-scaled versions of each other. We discuss various consistency checks relating to the galaxy modeling and starlight contributions, as well as possible systematic errors in the current set of reverberation measurements from which we determine the form of the R BLR-L relationship.

Chromatin organization marks exon-intron structure.

Abstract: An increasing body of evidence indicates that transcription and splicing are coupled, and it is accepted that chromatin organization regulates transcription. Little is known about the cross-talk between chromatin structure and exon-intron architecture. By analysis of genome-wide nucleosome-positioning data sets from humans, flies and worms, we found that exons show increased nucleosome-occupancy levels with respect to introns, a finding that we link to differential GC content and nucleosome-disfavoring elements between exons and introns. Analysis of genome-wide chromatin immunoprecipitation data in humans and mice revealed four specific post-translational histone modifications enriched in exons. Our findings indicate that previously described enrichment of H3K36me3 modifications in exons reflects a more fundamental phenomenon, namely increased nucleosome occupancy along exons. Our results suggest an RNA polymerase II-mediated cross-talk between chromatin structure and exon-intron architecture, implying that exon selection may be modulated by chromatin structure.

Drug-eluting medical devices

Abstract: Composite structures composed of a device as a core structure, being a medical device or article, and a porous polymeric coat and designed capable of encapsulating bioactive agents while retaining the activity of these agents are disclosed. Further disclosed are processes of preparing such composite structures.

Breast-feeding: A commentary by the ESPGHAN Committee on Nutrition

Abstract: This medical position article by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition summarises the current status of breast-feeding practice, the present knowledge on the composition of human milk, advisable duration of exclusive and partial breast-feeding, growth of the breast-fed infant, health benefits associated with breast-feeding, nutritional supplementation for breast-fed infants, and contraindications to breast-feeding. This article emphasises the important role of paediatricians in the implementation of health policies devised to promote breast-feeding.The European Society for Paediatric Gastroenterology, Hepatology, and Nutrition Committee on Nutrition recognises breast-feeding as the natural and advisable way of supporting the healthy growth and development of young children. This article delineates the health benefits of breast-feeding, reduced risk of infectious diarrhoea and acute otitis media being the best documented. Exclusive breast-feeding for around 6 months is a desirable goal, but partial breast-feeding as well as breast-feeding for shorter periods of time are also valuable. Continuation of breast-feeding after the introduction of complementary feeding is encouraged as long as mutually desired by mother and child.The role of health care workers, including paediatricians, is to protect, promote, and support breast-feeding. Health care workers should be trained in breast-feeding issues and counselling, and they should encourage practices that do not undermine breast-feeding. Societal standards and legal regulations that facilitate breast-feeding should be promoted, such as providing maternity leave for at least 6 months and protecting working mothers.

DAP‐kinase‐mediated phosphorylation on the BH3 domain of beclin 1 promotes dissociation of beclin 1 from Bcl‐XL and induction of autophagy

Abstract: Autophagy, an evolutionarily conserved process, has functions both in cytoprotective and programmed cell death mechanisms. Beclin 1, an essential autophagic protein, was recently identified as a BH3-domain-only protein that binds to Bcl-2 anti-apoptotic family members. The dissociation of beclin 1 from its Bcl-2 inhibitors is essential for its autophagic activity, and therefore should be tightly controlled. Here, we show that death-associated protein kinase (DAPK) regulates this process. The activated form of DAPK triggers autophagy in a beclin-1-dependent manner. DAPK phosphorylates beclin 1 on Thr 119 located at a crucial position within its BH3 domain, and thus promotes the dissociation of beclin 1 from Bcl-XL and the induction of autophagy. These results reveal a substrate for DAPK that acts as one of the core proteins of the autophagic machinery, and they provide a new phosphorylation-based mechanism that reduces the interaction of beclin 1 with its inhibitors to activate the autophagic machinery.

SPITZER QUASAR AND ULIRG EVOLUTION STUDY (QUEST). IV. COMPARISON OF 1 Jy ULTRALUMINOUS INFRARED GALAXIES WITH PALOMAR-GREEN QUASARS

Abstract: We report the results from a comprehensive study of 74 ultraluminous infrared galaxies (ULIRGs) and 34 Palomar-Green (PG) quasars within z ~ 0.3 observed with the Spitzer Infrared Spectrograph (IRS). The contribution of nuclear activity to the bolometric luminosity in these systems is quantified using six independent methods that span a range in wavelength and give consistent results within ~±10%-15% on average. This agreement suggests that deeply buried active galactic nuclei (AGNs) invisible to Spitzer IRS but bright in the far-infrared are not common in this sample. The average derived AGN contribution in ULIRGs is ~35%-40%, ranging from ~15%-35% among "cool" (f_(25)/f_(60) ≤ 0.2) optically classified H II-like and LINER ULIRGs to ~50 and ~75% among warm Seyfert 2 and Seyfert 1 ULIRGs, respectively. This number exceeds ~80% in PG QSOs. ULIRGs fall in one of three distinct AGN classes: (1) objects with small extinctions and large polycyclic aromatic hydrocarbon (PAH) equivalent widths are highly starburst-dominated; (2) systems with large extinctions and modest PAH equivalent widths have larger AGN contributions, but still tend to be starburst-dominated; and (3) ULIRGs with both small extinctions and small PAH equivalent widths host AGN that are at least as powerful as the starbursts. The AGN contributions in class 2 ULIRGs are more uncertain than in the other objects, and we cannot formally rule out the possibility that these objects represent a physically distinct type of ULIRGs. A morphological trend is seen along the sequence (1)-(2)-(3), in general agreement with the standard ULIRG–QSO evolution scenario and suggestive of a broad peak in extinction during the intermediate stages of merger evolution. However, the scatter in this sequence, including the presence of a significant number of AGN-dominated systems prior to coalescence and starburst-dominated but fully merged systems, implies that black hole accretion, in addition to depending on the merger phase, also has a strong chaotic/random component, as in local AGNs.

Adaptive Prediction of Environmental Changes by Microorganisms

Abstract: Natural habitats of some microorganisms may fluctuate erratically, whereas others, which are more predictable, offer the opportunity to prepare in advance for the next environmental change. In analogy to classical Pavlovian conditioning, microorganisms may have evolved to anticipate environmental stimuli by adapting to their temporal order of appearance. Here we present evidence for environmental change anticipation in two model microorganisms, Escherichia coli and Saccharomyces cerevisiae. We show that anticipation is an adaptive trait, because pre-exposure to the stimulus that typically appears early in the ecology improves the organism's fitness when encountered with a second stimulus. Additionally, we observe loss of the conditioned response in E. coli strains that were repeatedly exposed in a laboratory evolution experiment only to the first stimulus. Focusing on the molecular level reveals that the natural temporal order of stimuli is embedded in the wiring of the regulatory network-early stimuli pre-induce genes that would be needed for later ones, yet later stimuli only induce genes needed to cope with them. Our work indicates that environmental anticipation is an adaptive trait that was repeatedly selected for during evolution and thus may be ubiquitous in biology.

Domain adaptation: Learning bounds and algorithms

Abstract: This paper addresses the general problem of domain adaptation which arises in a variety of applications where the distribution of the labeled sample available somewhat differs from that of the test data. Building on previous work by Ben-David et al. (2007), we introduce a novel distance between distributions, discrepancy distance, that is tailored to adaptation problems with arbitrary loss functions. We give Rademacher complexity bounds for estimating the discrepancy distance from finite samples for different loss functions. Using this distance, we derive new generalization bounds for domain adaptation for a wide family of loss functions. We also present a series of novel adaptation bounds for large classes of regularization-based algorithms, including support vector machines and kernel ridge regression based on the empirical discrepancy. This motivates our analysis of the problem of minimizing the empirical discrepancy for various loss functions for which we also give several algorithms. We report the results of preliminary experiments that demonstrate the benefits of our discrepancy minimization algorithms for domain adaptation.

Fiat-Shamir with Aborts: Applications to Lattice and Factoring-Based Signatures

Abstract: We demonstrate how the framework that is used for creating efficient number-theoretic ID and signature schemes can be transferred into the setting of lattices. This results in constructions of the most efficient to-date identification and signature schemes with security based on the worst-case hardness of problems in ideal lattices. In particular, our ID scheme has communication complexity of around 65,000 bits and the length of the signatures produced by our signature scheme is about 50,000 bits. All prior lattice-based identification schemes required on the order of millions of bits to be transferred, while all previous lattice-based signature schemes were either stateful, too inefficient, or produced signatures whose lengths were also on the order of millions of bits. The security of our identification scheme is based on the hardness of finding the approximate shortest vector to within a factor of $\tilde{O}(n^2)$ in the standard model, while the security of the signature scheme is based on the same assumption in the random oracle model. Our protocols are very efficient, with all operations requiring $\tilde{O}(n)$ time. We also show that the technique for constructing our lattice-based schemes can be used to improve certain number-theoretic schemes. In particular, we are able to shorten the length of the signatures that are produced by Girault's factoring-based digital signature scheme ([10][11][31]).

Common variants at five new loci associated with early-onset inflammatory bowel disease.

Abstract: The inflammatory bowel diseases (IBD) Crohn's disease and ulcerative colitis are common causes of morbidity in children and young adults in the western world. Here we report the results of a genome-wide association study in early-onset IBD involving 3,426 affected individuals and 11,963 genetically matched controls recruited through international collaborations in Europe and North America, thereby extending the results from a previous study of 1,011 individuals with early-onset IBD. We have identified five new regions associated with early-onset IBD susceptibility, including 16p11 near the cytokine gene IL27 (rs8049439, P = 2.41 x 10(-9)), 22q12 (rs2412973, P = 1.55 x 10(-9)), 10q22 (rs1250550, P = 5.63 x 10(-9)), 2q37 (rs4676410, P = 3.64 x 10(-8)) and 19q13.11 (rs10500264, P = 4.26 x 10(-10)). Our scan also detected associations at 23 of 32 loci previously implicated in adult-onset Crohn's disease and at 8 of 17 loci implicated in adult-onset ulcerative colitis, highlighting the close pathogenetic relationship between early- and adult-onset IBD.

Super-Resolution in Medical Imaging

Abstract: This paper provides an overview on super-resolution (SR) research in medical imaging applications Many imaging modalities exist Some provide anatomical information and reveal information about the structure of the human body, and others provide functional information, locations of activity for specific activities and specified tasks Each imaging system has a characteristic resolution, which is determined based on physical constraints of the system detectors that are in turn tuned to signal-to-noise and timing considerations A common goal across systems is to increase the resolution, and as much as possible achieve true isotropic 3-D imaging SR technology can serve to advance this goal Research on SR in key medical imaging modalities, including MRI, fMRI and PET, has started to emerge in recent years and is reviewed herein The algorithms used are mostly based on standard SR algorithms Results demonstrate the potential in introducing SR techniques into practical medical applications

Familial adenomatous polyposis.

Abstract: Familial adenomatous polyposis (FAP) is characterized by the development of many tens to thousands of adenomas in the rectum and colon during the second decade of life. FAP has an incidence at birth of about 1/8,300, it manifests equally in both sexes, and accounts for less than 1% of colorectal cancer (CRC) cases. In the European Union, prevalence has been estimated at 1/11,300-37,600. Most patients are asymptomatic for years until the adenomas are large and numerous, and cause rectal bleeding or even anemia, or cancer develops. Generally, cancers start to develop a decade after the appearance of the polyps. Nonspecific symptoms may include constipation or diarrhea, abdominal pain, palpable abdominal masses and weight loss. FAP may present with some extraintestinal manifestations such as osteomas, dental abnormalities (unerupted teeth, congenital absence of one or more teeth, supernumerary teeth, dentigerous cysts and odontomas), congenital hypertrophy of the retinal pigment epithelium (CHRPE), desmoid tumors, and extracolonic cancers (thyroid, liver, bile ducts and central nervous system). A less aggressive variant of FAP, attenuated FAP (AFAP), is characterized by fewer colorectal adenomatous polyps (usually 10 to 100), later age of adenoma appearance and a lower cancer risk. Some lesions (skull and mandible osteomas, dental abnormalities, and fibromas on the scalp, shoulders, arms and back) are indicative of the Gardner variant of FAP. Classic FAP is inherited in an autosomal dominant manner and results from a germline mutation in the adenomatous polyposis (APC) gene. Most patients (~70%) have a family history of colorectal polyps and cancer. In a subset of individuals, a MUTYH mutation causes a recessively inherited polyposis condition, MUTYH-associated polyposis (MAP), which is characterized by a slightly increased risk of developing CRC and polyps/adenomas in both the upper and lower gastrointestinal tract. Diagnosis is based on a suggestive family history, clinical findings, and large bowel endoscopy or full colonoscopy. Whenever possible, the clinical diagnosis should be confirmed by genetic testing. When the APC mutation in the family has been identified, genetic testing of all first-degree relatives should be performed. Presymptomatic and prenatal (amniocentesis and chorionic villous sampling), and even preimplantation genetic testing is possible. Referral to a geneticist or genetic counselor is mandatory. Differential diagnoses include other disorders causing multiple polyps (such as Peutz-Jeghers syndrome, familial juvenile polyps or hyperplastic polyposis, hereditary mixed polyposis syndromes, and Lynch syndrome). Cancer prevention and maintaining a good quality of life are the main goals of management and regular and systematic follow-up and supportive care should be offered to all patients. By the late teens or early twenties, colorectal cancer prophylactic surgery is advocated. The recommended alternatives are total proctocolectomy and ileoanal pouch or ileorectal anastomosis for AFAP. Duodenal cancer and desmoids are the two main causes of mortality after total colectomy, they need to be identified early and treated. Upper endoscopy is necessary for surveillance to reduce the risk of ampullary and duodenal cancer. Patients with progressive tumors and unresectable disease may respond or stabilize with a combination of cytotoxic chemotherapy and surgery (when possible to perform). Adjunctive therapy with celecoxib has been approved by the US Food and Drug Administration and the European Medicines Agency in patients with FAP. Individuals with FAP carry a 100% risk of CRC; however, this risk is reduced significantly when patients enter a screening-treatment program.

Nonlinear generation and manipulation of Airy beams

Abstract: Airy beams have so far been generated by linear diffractive elements. Now, scientists show that they can also be created by a nonlinear process, opening the door to all-optical beam control and production at wavelengths unavailable by conventional methods.

Amyloid-beta as a positive endogenous regulator of release probability at hippocampal synapses.

Abstract: Accumulation of cerebral amyloid-beta peptide (Abeta) is essential for developing synaptic and cognitive deficits in Alzheimer's disease. However, the physiological functions of Abeta, as well as the primary mechanisms that initiate early Abeta-mediated synaptic dysfunctions, remain largely unknown. Here we examine the acute effects of endogenously released Abeta peptides on synaptic transfer at single presynaptic terminals and synaptic connections in rodent hippocampal cultures and slices. Increasing extracellular Abeta by inhibiting its degradation enhanced release probability, boosting ongoing activity in the hippocampal network. Presynaptic enhancement mediated by Abeta was found to depend on the history of synaptic activation, with lower impact at higher firing rates. Notably, both elevation and reduction in Abeta levels attenuated short-term synaptic facilitation during bursts in excitatory synaptic connections. These observations suggest that endogenous Abeta peptides have a crucial role in activity-dependent regulation of synaptic vesicle release and might point to the primary pathological events that lead to compensatory synapse loss in Alzheimer's disease.